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1.
Nutrients ; 16(7)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38613029

RESUMEN

Methionine dependence is a characteristic of most cancer cells where they are unable to proliferate when the essential amino acid methionine is replaced with its precursor homocysteine in the growing media. Normal cells, on the other hand, thrive under these conditions and are referred to as methionine-independent. The reaction that adds a methyl group from 5-methyltetrahydrofolate to homocysteine to regenerate methionine is catalyzed by the enzyme methionine synthase with the cofactor cobalamin (vitamin B12). However, decades of research have shown that methionine dependence in cancer is not due to a defect in the activity of methionine synthase. Cobalamin metabolism has been tied to the dependent phenotype in rare cell lines. We have identified a human colorectal cancer cell line in which the cells regain the ability to proliferation in methionine-free, L-homocystine-supplemented media when cyanocobalamin is supplemented at a level of 1 µg/mL. In human SW48 cells, methionine replacement with L-homocystine does not induce any measurable increase in apoptosis or reactive oxygen species production in this cell line. Rather, proliferation is halted, then restored in the presence of cyanocobalamin. Our data show that supplementation with cyanocobalamin prevents the activation of the integrated stress response (ISR) in methionine-deprived media in this cell line. The ISR-associated cell cycle arrest, characteristic of methionine-dependence in cancer, is also prevented, leading to the continuation of proliferation in methionine-deprived SW48 cells with cobalamin. Our results highlight differences between cancer cell lines in the response to cobalamin supplementation in the context of methionine dependence.


Asunto(s)
Neoplasias Colorrectales , Metionina , Humanos , Metionina/farmacología , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa , Vitamina B 12/farmacología , Homocistina , Racemetionina , Línea Celular , Homocisteína , Neoplasias Colorrectales/tratamiento farmacológico
2.
J Nutr Sci Vitaminol (Tokyo) ; 70(2): 139-149, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38684384

RESUMEN

Since propionate exerts several physiological effects, maintenance of its normal colonic fermentation is essential. To investigate whether vitamin B12 (VB12) is essential for normal propionate fermentation by colonic bacteria, via the succinate pathway, we examined if high-amylose cornstarch (HACS) feeding activated such a pathway, if high HACS feeding impaired propionate fermentation, and if oral VB12 supplementation normalized propionate fermentation. Male rats were given control, 20% HACS or 3% fucose diets (Expt. 1); a VB12-free control diet or one supplemented with 5-30% HACS (Expt. 2); and the 20% HACS diet supplemented with 0.025-25 mg/kg of VB12 (Expt. 3), for 14 d. HACS feeding significantly increased cecal succinate concentration, activating the succinate pathway (Expt. 1). Cecal cobalamin concentration in 20% and 30% HACS groups was about 75% of that in the control group (Expt. 2). Cecal succinate and propionate concentrations significantly increased and decreased in 30% HACS groups, respectively, compared with the control group. Although HACS group supplemented with 0.025 mg/kg of VB12 had a low concentration of cecal propionate, adding high amounts of VB12 to HACS diets provided sufficient amounts of VB12 to rat ceca and increased cecal propionate concentration (Expt. 3). Compared with the non-HACS group, the relative abundance of Akkermansia muciniphila, but not Bacteroides/Phocaeicola, was lower in the HACS counterpart and showed improvement with increased VB12 doses. To summarize, feeding high HACS decreased and increased cecal VB12 and succinate concentrations, respectively. Furthermore, colonic delivery of sufficient amounts of VB12 to rats likely reduced accumulation of succinate and normalized propionate fermentation.


Asunto(s)
Amilosa , Ciego , Colon , Suplementos Dietéticos , Fermentación , Propionatos , Almidón , Vitamina B 12 , Animales , Masculino , Propionatos/metabolismo , Ciego/microbiología , Ciego/metabolismo , Vitamina B 12/administración & dosificación , Vitamina B 12/farmacología , Colon/metabolismo , Colon/microbiología , Almidón/metabolismo , Almidón/administración & dosificación , Amilosa/administración & dosificación , Amilosa/metabolismo , Ratas , Ácido Succínico/metabolismo , Dieta , Ratas Wistar , Ratas Sprague-Dawley
3.
J Anim Sci ; 1022024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38407272

RESUMEN

We hypothesized that restricted maternal nutrition and supplementation of one-carbon metabolites (OCM; methionine, folate, choline, and vitamin B12) would affect placental vascular development during early pregnancy. A total of 43 cows were bred, and 32 heifers successfully became pregnant with female calves, leading to the formation of four treatment groups: CON - OCM (n = 8), CON + OCM (n = 7), RES - OCM (n = 9), and RES + OCM (n = 8). The experimental design was a 2 × 2 factorial, with main factors of dietary intake affecting average daily gain: control (CON; 0.6 kg/d ADG) and restricted (RES; -0.23 kg/d ADG); and OCM supplementation (+OCM) in which the heifers were supplemented with rumen-protected methionine (7.4 g/d) and choline (44.4 g/d) and received weekly injections of 320 mg of folate and 20 mg of vitamin B12, or received no supplementation (-OCM; corn carrier and saline injections). Heifers were individually fed and randomly assigned to treatment at breeding (day 0). Placentomes were collected on day 63 of gestation (0.225 of gestation). Fluorescent staining with CD31 and CD34 combined with image analysis was used to determine the vascularity of the placenta. Images were analyzed for capillary area density (CAD) and capillary number density (CND). Areas evaluated included fetal placental cotyledon (COT), maternal placental caruncle (CAR), whole placentome (CAR + COT), intercotyledonary fetal membranes (ICOT, or chorioallantois), intercaruncular endometrium (ICAR), and endometrial glands (EG). Data were analyzed with the GLM procedure of SAS, with heifer as the experimental unit and significance at P ≤ 0.05 and a tendency at P > 0.05 and P < 0.10. Though no gain × OCM interactions existed (P ≥ 0.10), OCM supplementation increased (P = 0.01) CAD of EG, whereas nutrient restriction tended (P < 0.10) to increase CAD of ICOT and CND of COT. Additionally, there was a gain × OCM interaction (P < 0.05) for CAD within the placentome and ICAR, such that RES reduced and supplementation of RES with OCM restored CAD. These results indicate that maternal rate of gain and OCM supplementation affected placental vascularization (capillary area and number density), which could affect placental function and thus the efficiency of nutrient transfer to the fetus during early gestation.


In cow­calf production, periods of poor forage availability or quality can result in nutrient restriction during pregnancy. Previous studies have shown that even moderate maternal feed restriction during pregnancy, including very early in pregnancy, has profound effects on fetal and placental development, potentially having lasting impacts on calf growth and body composition later in life. One-carbon metabolites (OCM) in the diet are biomolecules required for methylation reactions and participate in the regulation of gene expression. Our objective was to evaluate the effects of nutrient restriction and OCM supplementation (specifically methionine, choline, folate, and vitamin B12) on placental vascular development during early pregnancy. Proper placental vascular development is necessary for healthy pregnancy outcomes, reflected by normal birth weight and healthy offspring. Our results indicated that maternal rate of gain and OCM supplementation affect placental vascularization, which could affect placental function and thereby fetal development throughout gestation. In the context of beef cattle production, our study sheds light on strategies that could enhance placental vascular development during early pregnancy. However, it is essential to recognize the nuances in our data, highlighting the need for further research to fully comprehend these intricate processes.


Asunto(s)
Complejo Hierro-Dextran , Placenta , Femenino , Embarazo , Animales , Bovinos , Fitomejoramiento , Metionina/farmacología , Racemetionina , Carbono , Colina/farmacología , Suplementos Dietéticos , Ácido Fólico/farmacología , Vitamina B 12/farmacología , Dieta/veterinaria
5.
J Anim Physiol Anim Nutr (Berl) ; 108(3): 635-645, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38197588

RESUMEN

Biotin (BI) and cobalamin (CA) are essential for rumen propionate production and hepatic gluconeogenesis. The study evaluated the influence of BI or/and coated CA (CCA) on milk performance and nutrient digestion in cows. Sixty Holstein dairy cows were assigned in a 2 × 2 factorial arrangement and randomised block design to four groups. The factors were BI at 0 or 20 mg/day and CCA at 0 or 9 mg CA/day. Dry matter intake increased with BI addition but was unchanged with CCA supply. Addition of BI or CCA increased fat-corrected milk, milk fat and milk protein yields and feed efficiency. Moreover, lactose yield was increased by CCA addition. Dry matter, organic matter, crude protein and acid detergent fibre total-tract digestibility increased for BI or CCA supply. When CCA was supplemented, positive response of neutral detergent fibre digestibility to BI addition was enhanced. Supplementing BI did not affect pH, propionate content and acetate to propionate ratio, but increased total volatile fatty acids (VFA) and acetate contents. Supplementing CCA decreased pH and acetate to propionate ratio, but increased total VFA, acetate and propionate contents. Rumen protease and carboxymethyl-cellulase activities and fungi, bacteria and Butyrivibrio fibrisolvens numbers increased for BI or CCA supply. In addition, protozoa increased for BI addition, and protease activity and Prevotella ruminicola increased for CCA supply. When CCA was supplemented, positive responses of R. albus and Ruminobacter amylophilus numbers to BI addition were enhanced. Blood glucose concentration was unchanged with BI supply, but increased for CCA supply. Blood nonesterified fatty acids and ß-hydroxybutyrate contents reduced with BI or CCA supply. Supplementation with BI or CCA increased blood BI or CA content. The results showed that supplementing BI or/and CCA improved lactation performance and nutrient digestion, and CCA supply did not enhance the lactation performance response to BI supply.


Asunto(s)
Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Biotina , Dieta , Digestión , Fermentación , Lactancia , Rumen , Vitamina B 12 , Animales , Bovinos/fisiología , Femenino , Rumen/efectos de los fármacos , Rumen/fisiología , Lactancia/efectos de los fármacos , Lactancia/fisiología , Digestión/efectos de los fármacos , Alimentación Animal/análisis , Dieta/veterinaria , Fermentación/efectos de los fármacos , Biotina/administración & dosificación , Biotina/farmacología , Vitamina B 12/farmacología , Vitamina B 12/administración & dosificación , Suplementos Dietéticos , Leche/química
6.
Artículo en Inglés | MEDLINE | ID: mdl-38231988

RESUMEN

Subacute combined degeneration (SCD) of the spinal cord is a disease involving the lateral and posterior columns of the spinal cord that can manifest in patients with vitamin B12 deficiency. Nitrous oxide (N2O)-induced SCD of the spinal cord is a result of N2O interfering with the metabolism of vitamin B12 and results in nervous system demyelination. This is an infrequent complication of N2O anesthesia; however, cases are rising with recreational N2O use. This case report describes a patient with SCD of the spinal cord induced by recreational N2O abuse. The patient presented to a spine surgery clinic with a 3-week history of progressive global weakness and paresthesias. After a detailed history and physical examination, the diagnosis was made and supported by various tests and imaging findings. Despite marked neurologic deficits, the patient's symptoms improved markedly with therapy and vitamin B12 supplementation. Spine surgery clinicians may be confronted with these cases and should be aware of this atypical presentation of SCD. As in our case, patients may present with neurologic deficits of unclear etiology. Neurologic dysfunction may be irreversible; therefore, accurate diagnosis, medical treatment, and complete neurologic evaluation are of the utmost importance to prevent additional progression.


Asunto(s)
Degeneración Combinada Subaguda , Trastornos Relacionados con Sustancias , Deficiencia de Vitamina B 12 , Humanos , Degeneración Combinada Subaguda/inducido químicamente , Degeneración Combinada Subaguda/complicaciones , Óxido Nitroso/efectos adversos , Deficiencia de Vitamina B 12/inducido químicamente , Deficiencia de Vitamina B 12/tratamiento farmacológico , Deficiencia de Vitamina B 12/complicaciones , Vitamina B 12/uso terapéutico , Vitamina B 12/farmacología , Trastornos Relacionados con Sustancias/complicaciones
7.
Chem Biol Interact ; 387: 110823, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38049026

RESUMEN

Chronic hyperglycemia-induced neuropathological changes include neuronal apoptosis, astrogliosis, decrease in neurotrophic support, impaired synaptic plasticity, and impaired protein quality control (PQC) system. Vitamin B12 is indispensable for neuronal development and brain function. Several studies reported the neuroprotective effect of B12 supplementation in diabetic patients. However, the underlying molecular basis for the neuroprotective effect of B12 supplementation in diabetes needs to be thoroughly investigated. Two-month-old Sprague-Dawley rats were randomly assigned into three groups: Control (CN), diabetes (D; induced with streptozotocin; STZ), and diabetic rats supplemented with vitamin B12 (DBS; vitamin B12; 50 µg/kg) for four months. At the end of 4 months of experimentation, the brain was dissected to collect the cerebral cortex (CC). The morphology of CC was investigated with H&E and Nissl body staining. Neuronal apoptosis was determined with TUNEL assay. The components of neurotrophic support, astrogliosis, synaptic plasticity, and PQC processes were investigated by immunoblotting and immunostaining methods. H& E, Nissl body, and TUNEL staining revealed that diabetes-induced neuronal apoptosis and degeneration. However, B12 supplementation ameliorated the diabetes-induced neuronal apoptosis. Further, B12 supplementation restored the markers of neurotrophic support (BDNF, NGF, and GDNF), and synaptic plasticity (SYP, and PSD-95) in diabetic rats. Interestingly, B12 supplementation also attenuated astrogliosis, ER stress, and ameliorated autophagy-related proteins in diabetic rats. Overall, these findings suggest that B12 acts as a neuroprotective agent by inhibiting the neuropathological changes in STZ-induced type 1 diabetes. Thus, B12 supplementation could produce beneficial outcomes including neuroprotective effects in diabetic patients.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Fármacos Neuroprotectores , Ratas , Humanos , Animales , Lactante , Vitamina B 12/farmacología , Vitamina B 12/uso terapéutico , Ratas Sprague-Dawley , Estreptozocina/farmacología , Diabetes Mellitus Experimental/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Gliosis , Apoptosis
8.
Poult Sci ; 103(1): 103262, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38007902

RESUMEN

This study aimed to determine phosphorus and vitamin B12 supplementation effect in semen extender on the quality and fertility ability of chilled Thai native rooster semen. Eighty-four ejaculates of semen from 26 Thai native roosters (Burmese × Vietnam crossbreed) were included. Semen was collected by applying dorsal-abdominal massage once a week, pooled, diluted to 500 million sperms per dose, and divided into 6 groups. The semen samples used for control group were diluted with modified Beltsville poultry semen extender (BPSE). For the treatment groups 2 to 6: semen samples were diluted with modified BPSE and enriched with phosphorus and vitamin B12 (Octafos Octa Memorial Co., Ltd., Bangkok, Thailand) at concentrations 0.02, 0.04, 0.06, 0.08, and 0.10%. Semen fertility ability was tested in 6 replications by inseminating layer hens. Thirty-six Thai native hens were randomly assigned to 3 groups (control, 0.04, and 0.08%) of 12 hens and were inseminated with a dose of 0.2 mL on collecting day. Sperm motion characteristics (i.e., sperm motility, sperm progressive motility, and sperm kinetic parameters) were measured using a computer-assisted sperm analysis system (SCA, Proiser S.L., Valencia, Spain). Sperm viability, mitochondrial activity, acrosome integrity, plasma membrane integrity, and malondialdehyde (MDA) concentration were also evaluated. The sperm motion characteristics were the highest in the 0.04% supplementation group on all days of collection, especially the VCL and VAP (P < 0.05). The viability, mitochondrial activity, plasma membrane and acrosome integrity of spermatozoa were greater in the 0.04% supplementation group than in the control groups (P < 0.05). The 0.04% supplementation group had the lowest MDA concentration in all days of collection. The 0.04% supplementation group were higher both fertility (66.59 vs. 48.50%: P < 0.05) and hatching rates (58.80 vs. 43.18%: P < 0.05) than in the control group. In conclusion, 0.04% phosphorus and vitamin B12 concentrations supplementation in semen extender improved rooster semen quality and fertility in chilled rooster semen.


Asunto(s)
Preservación de Semen , Semen , Masculino , Animales , Femenino , Pollos , Análisis de Semen/veterinaria , Tailandia , Vitamina B 12/farmacología , Vitamina B 12/metabolismo , Motilidad Espermática , Preservación de Semen/veterinaria , Crioprotectores/farmacología , Criopreservación/veterinaria , Espermatozoides , Suplementos Dietéticos
9.
Int J Food Microbiol ; 410: 110486, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-37992553

RESUMEN

Listeria monocytogenes is a facultative anaerobe which can cause a severe food-borne infection known as listeriosis. L. monocytogenes is capable of utilizing various nutrient sources including rhamnose, a naturally occurring deoxy sugar abundant in foods. L. monocytogenes can degrade rhamnose into lactate, acetate and 1,2-propanediol. Our previous study showed that addition of vitamin B12 stimulated anaerobic growth of L. monocytogenes on rhamnose due to the activation of bacterial microcompartments for 1,2-propanediol utilization (pdu BMC) with concomitant production of propionate and propanol. Notably, anaerobic 1,2-propanediol metabolism has been linked to virulence of enteric pathogens including Salmonella spp. and L. monocytogenes. In this study we investigated the impact of B12 and BMC activation on i) aerobic and anerobic growth of L. monocytogenes on rhamnose and ii) the level of virulence. We observed B12-induced pdu BMC activation and growth stimulation only in anaerobically grown cells. Comparative Caco-2 virulence assays showed that these pdu BMC-induced cells have significantly higher translocation efficiency compared to non-induced cells (anaerobic growth without B12; aerobic growth with or without B12), while adhesion and invasion capacity is similar for all cells. Comparative proteome analysis showed specific and overlapping responses linked to metabolic shifts, activation of stress defense proteins and virulence factors, with RNA polymerase sigma factor SigL, teichoic acid export ATP-binding protein TagH, DNA repair and protection proteins, RadA and DPS, and glutathione synthase GshAB, previously linked to activation of virulence response in L. monocytogenes, uniquely upregulated in anaerobically rhamnose grown pdu-induced cells. Our results shed light on possible effects of B12 on L. monocytogenes competitive fitness and virulence activation when utilizing rhamnose in anaerobic conditions encountered during transmission and the human intestine.


Asunto(s)
Listeria monocytogenes , Listeriosis , Humanos , Ramnosa/metabolismo , Células CACO-2 , Propilenglicol/metabolismo , Virulencia/genética , Vitamina B 12/farmacología , Vitamina B 12/metabolismo , Listeriosis/microbiología , Vitaminas/metabolismo , Proteínas Bacterianas/genética
10.
Cell Rep ; 42(12): 113545, 2023 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-38064339

RESUMEN

Vitamin B12 (B12) deficiency causes neurological manifestations resembling multiple sclerosis (MS); however, a molecular explanation for the similarity is unknown. FTY720 (fingolimod) is a sphingosine 1-phosphate (S1P) receptor modulator and sphingosine analog approved for MS therapy that can functionally antagonize S1P1. Here, we report that FTY720 suppresses neuroinflammation by functionally and physically regulating the B12 pathways. Genetic and pharmacological S1P1 inhibition upregulates a transcobalamin 2 (TCN2)-B12 receptor, CD320, in immediate-early astrocytes (ieAstrocytes; a c-Fos-activated astrocyte subset that tracks with experimental autoimmune encephalomyelitis [EAE] severity). CD320 is also reduced in MS plaques. Deficiency of CD320 or dietary B12 restriction worsens EAE and eliminates FTY720's efficacy while concomitantly downregulating type I interferon signaling. TCN2 functions as a chaperone for FTY720 and sphingosine, whose complex induces astrocytic CD320 internalization, suggesting a delivery mechanism of FTY720/sphingosine via the TCN2-CD320 pathway. Taken together, the B12-TCN2-CD320 pathway is essential for the mechanism of action of FTY720.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Animales , Clorhidrato de Fingolimod/farmacología , Clorhidrato de Fingolimod/uso terapéutico , Clorhidrato de Fingolimod/metabolismo , Astrocitos/metabolismo , Esfingosina/metabolismo , Vitamina B 12/farmacología , Vitamina B 12/uso terapéutico , Vitamina B 12/metabolismo , Transcobalaminas/metabolismo , Transcobalaminas/uso terapéutico , Glicoles de Propileno/metabolismo , Glicoles de Propileno/farmacología , Glicoles de Propileno/uso terapéutico , Vitaminas , Inmunosupresores/farmacología , Receptores de Lisoesfingolípidos/metabolismo
11.
Nutrients ; 15(24)2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38140305

RESUMEN

Background: Prolonged metformin treatment decreases vitamin B12 (B12) levels, whereas low B12 is associated with dyslipidaemia. Some studies have reported that metformin has no effect on intrahepatic triglyceride (TG) levels. Although AMP-activated protein kinase (AMPK) activation via adiponectin lowers hepatic TG content, its role in B12 deficiency and metformin has not been explored. We investigated whether low B12 impairs the beneficial effect of metformin on hepatic lipid metabolism via the AMPK-adiponectin axis. Methods: HepG2 was cultured using custom-made B12-deficient Eagle's Minimal Essential Medium (EMEM) in different B12-medium concentrations, followed by a 24-h metformin/adiponectin treatment. Gene and protein expressions and total intracellular TG were measured, and radiochemical analysis of TG synthesis and seahorse mitochondria stress assay were undertaken. Results: With low B12, total intracellular TG and synthesized radiolabelled TG were increased. Regulators of lipogenesis, cholesterol and genes regulating fatty acids (FAs; TG; and cholesterol biosynthesis were increased. FA oxidation (FAO) and mitochondrial function were decreased, with decreased pAMPKα and pACC levels. Following metformin treatment in hepatocytes with low B12, the gene and protein expression of the above targets were not alleviated. However, in the presence of adiponectin, intrahepatic lipid levels with low B12 decreased via upregulated pAMPKα and pACC levels. Again, combined adiponectin and metformin treatment ameliorated the low B12 effect and resulted in increased pAMPKα and pACC, with a subsequent reduction in lipogenesis, increased FAO and mitochondrion function. Conclusions: Adiponectin co-administration with metformin induced a higher intrahepatic lipid-lowering effect. Overall, we emphasize the potential therapeutic implications for hepatic AMPK activation via adiponectin for a clinical condition associated with B12 deficiency and metformin treatment.


Asunto(s)
Enfermedades Metabólicas , Metformina , Enfermedad del Hígado Graso no Alcohólico , Humanos , Metformina/farmacología , Células Hep G2 , Proteínas Quinasas Activadas por AMP/metabolismo , Adiponectina/metabolismo , Vitamina B 12/farmacología , Vitamina B 12/metabolismo , Hígado/metabolismo , Metabolismo de los Lípidos , Ácidos Grasos/metabolismo , Enfermedades Metabólicas/metabolismo , Colesterol/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo
12.
J Am Chem Soc ; 145(41): 22609-22619, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37803879

RESUMEN

Cerebral ischemia-reperfusion injury (CIRI) is often accompanied by upregulation of homocysteine (Hcy). Excessive Hcy damages cerebral vascular endothelial cells and neurons, inducing neurotoxicity and even neurodegeneration. Normally, supplementation of vitamin B12 is an ideal intervention to reduce Hcy. However, vitamin B12 therapy is clinically inefficacious for CIRI. Considering oxidative stress is closely related to CIRI, the lysosome is the pivotal site for vitamin B12 transport. Lysosomal oxidative stress might hinder the transport of vitamin B12. Whether lysosomal malondialdehyde (lysosomal MDA), as the authoritative biomarker of lysosomal oxidative stress, interferes with the transport of vitamin B12 has not been elucidated. This is ascribed to the absence of effective methods for real-time and in situ measurement of lysosomal MDA within living brains. Herein, a fluorescence imaging agent, Lyso-MCBH, was constructed to specifically monitor lysosomal MDA by entering the brain and targeting the lysosome. Erupting the lysosomal MDA level in living brains of mice under CIRI was first observed using Lyso-MCBH. Excessive lysosomal MDA was found to affect the efficacy of vitamin B12 by blocking the transport of vitamin B12 from the lysosome to the cytoplasm. More importantly, the expression and function of the vitamin B12 transporter LMBD1 were proved to be associated with excessive lysosomal MDA. Altogether, the revealing of the lysosomal MDA-LMBD1 axis provides a cogent interpretation of the inefficacy of vitamin B12 in CIRI, which could be a prospective therapeutic target.


Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Animales , Ratones , Vitamina B 12/farmacología , Vitamina B 12/metabolismo , Malondialdehído/metabolismo , Células Endoteliales/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Lisosomas/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Vitaminas/metabolismo , Homocisteína/metabolismo
13.
Int J Mol Sci ; 24(20)2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37894898

RESUMEN

High glucose levels can lead to the apoptosis of islet ß cells, while autophagy can provide cytoprotection and promote autophagic cell death. Vitamin B12, a water-soluble B vitamin, has been shown to regulate insulin secretion and increase insulin sensitivity. However, the precise mechanism of action remains unclear. In this study, we investigated the influence of vitamin B12 on high glucose-induced apoptosis and autophagy in RIN-m5F cells to elucidate how vitamin B12 modulates insulin release. Our results demonstrate that exposure to 45 mM glucose led to a significant increase in the apoptosis rate of RIN-m5F cells. The treatment with vitamin B12 reduced the apoptosis rate and increased the number of autophagosomes. Moreover, vitamin B12 increased the ratio of microtubule-associated protein 1 light chain 3 beta to microtubule-associated protein 1 light chain 3 alpha (LC3-II/LC3-I), while decreasing the amount of sequestosome 1 (p62) and inhibiting the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K) under both normal- and high-glucose conditions. The additional experiments revealed that vitamin B12 inhibited high glucose-induced apoptosis. Notably, this protective effect was attenuated when the autophagy inhibitor 3-methyladenine was introduced. Our findings suggest that vitamin B12 protects islet ß cells against apoptosis induced by high glucose levels, possibly by inducing autophagy.


Asunto(s)
Glucosa , Vitamina B 12 , Vitamina B 12/farmacología , Glucosa/farmacología , Autofagia , Apoptosis , Proteínas Asociadas a Microtúbulos/metabolismo
14.
Nutrients ; 15(18)2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37764675

RESUMEN

Aging results in more health challenges, including neurodegeneration. Healthy aging is possible through nutrition as well as other lifestyle changes. One-carbon (1C) metabolism is a key metabolic network that integrates nutritional signals with several processes in the human body. Dietary supplementation of 1C components, such as folic acid, vitamin B12, and choline are reported to have beneficial effects on normal and diseased brain function. The aim of this review is to summarize the current clinical studies investigating dietary supplementation of 1C, specifically folic acid, choline, and vitamin B12, and its effects on healthy aging. Preclinical studies using model systems have been included to discuss supplementation mechanisms of action. This article will also discuss future steps to consider for supplementation. Dietary supplementation of folic acid, vitamin B12, or choline has positive effects on normal and diseased brain function. Considerations for dietary supplementation to promote healthy aging include using precision medicine for individualized plans, avoiding over-supplementation, and combining therapies.


Asunto(s)
Suplementos Dietéticos , Envejecimiento Saludable , Humanos , Ácido Fólico/farmacología , Encéfalo , Vitamina B 12/farmacología , Colina/farmacología
15.
Biochem Pharmacol ; 217: 115832, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37769712

RESUMEN

BACKGROUND: The present study aims to assess the effect of vitamin B12 (Vit B12) on depression-like behavior caused by nicotine (Nic) withdrawal, which is more likely due to the anxiogenic effect of Nic in adolescent male rats, through assessing behavioral and biochemical analysis. METHODS: Adolescent male rats were divided into vehicle (received normal saline), and experimental groups that received Nic (2 mg/kg, intraperitoneally (i.p.)) for three consecutive weeks and after that, the group that received normal saline was divided into two groups, one of which returned to a regular diet, and the second one received Vit B12 (1.5 mg/kg). The Nic group was divided into five groups, one of which received bupropion (Bup, 20 mg/kg), three of which received different doses of Vit B12 (0.5, 1, and 1.5 mg/kg), and the last one returned to a normal diet without treatment, which was considered as the withdrawal period. RESULTS: Behavioral analysis showed that Nic withdrawal induced anxiety and depression. Vit B12 and Bup reduced anxiety and depression induced by Nic withdrawal. The biochemical analysis demonstrated the more activity of oxidative stress factors and pro-inflammatory cytokines in which Nic was administered, whereas both Vit B12 and Bup reversed the results and improved the activity of both antioxidant and anti-inflammatory parameters. Furthermore, both serum and cortical Vit B12 levels dramatically decreased in nicotine group, whereas treatment with both Vit B12 and Bup as desirable treatments corrected Vit B12 levels. CONCLUSION: According to the present findings, the results revealed that Vit B12 is comparable with Bup in attenuation of Nic withdrawal symptoms. In addition, both Bup and Vit B12 improved the decreased serum and cortical levels of Vit B12, which caused by nicotine. Administration of Vit B12 in normal animals demonstrated better results in reducing antioxidant and anti-inflammatory parameters, which explores new hope to introduce Vit B12 as a novel antioxidant and anti-inflammatory agent to treat not only withdrawal, but also other diseases related to the prominent role of oxidative stress or inflammatory pathways, such as Alzheimer's disease.


Asunto(s)
Nicotina , Síndrome de Abstinencia a Sustancias , Ratas , Masculino , Animales , Vitamina B 12/farmacología , Vitamina B 12/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Solución Salina , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Antiinflamatorios , Estrés Oxidativo , Ansiedad/inducido químicamente , Ansiedad/tratamiento farmacológico , Vitaminas
16.
Essays Biochem ; 67(5): 853-863, 2023 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-37449444

RESUMEN

Methionine synthases (MetH) catalyse the methylation of homocysteine (Hcy) with 5-methyl-tetrahydrofolate (5, methyl-THF) acting as methyl donor, to form methionine (Met) and tetrahydrofolate (THF). This function is performed by two unrelated classes of enzymes that differ significantly in both their structures and mechanisms of action. The genomes of plants and many fungi exclusively encode cobalamin-independent enzymes (EC.2.1.1.14), while some fungi also possess proteins from the cobalamin-dependent (EC.2.1.1.13) family utilised by humans. Methionine synthase's function connects the methionine and folate cycles, making it a crucial node in primary metabolism, with impacts on important cellular processes such as anabolism, growth and synthesis of proteins, polyamines, nucleotides and lipids. As a result, MetHs are vital for the viability or virulence of numerous prominent human and plant pathogenic fungi and have been proposed as promising broad-spectrum antifungal drug targets. This review provides a summary of the relevance of methionine synthases to fungal metabolism, their potential as antifungal drug targets and insights into the structures of both classes of MetH.


Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa , Antifúngicos , Humanos , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/química , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/metabolismo , Virulencia , Tetrahidrofolatos/metabolismo , Vitamina B 12/metabolismo , Vitamina B 12/farmacología , Metionina/metabolismo
17.
J Exp Zool A Ecol Integr Physiol ; 339(9): 878-886, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37522473

RESUMEN

Vitamin B12 is a micronutrient required by a variety of organisms for healthy cellular functioning. Despite the systemic effects observed in cases of B12 deficiency, relatively little is known about how vitamin B12 affects immune health, especially in amphibians, which are declining at unprecedented rates. In this study, we tested how supplementing an algae diet with B12 affects the innate and adaptive immunity of Cuban tree frog (Osteopilus septentrionalis) tadpoles. We found that innate immunity, as measured by a bacterial killing assay, was significantly more robust in B12-supplemented tadpoles than control tadpoles, but no significant differences were found in natural antibody production or hematocrit between groups. Adaptive immunity, as measured by Aeromonas hydrophila-specific IgY antibodies, was significantly greater in tadpoles challenged with A. hydrophila and supplemented with B12 than in control tadpoles, those only challenged with A. hydrophila, and those only given B12. Our results suggest that vitamin B12 is an important factor in maintaining a functional immune system in tadpoles, which may also be true for all vertebrates.


Asunto(s)
Anuros , Vitamina B 12 , Animales , Larva/fisiología , Vitamina B 12/farmacología , Inmunidad Innata , Dieta/veterinaria
18.
Eur Rev Med Pharmacol Sci ; 27(11): 5240-5245, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37318498

RESUMEN

OBJECTIVE: The human papilloma virus (HPV) is the etiological agent of cervical cancer in more than 95% of cases worldwide. Although most HPV infections clear up on their own and most pre-cancerous lesions spontaneously resolve, in some cases, they can persist, leading to lesions which may progress towards invasive cervical cancer. MATERIALS AND METHODS: We evaluated the effects of the association of epigallocatechin gallate (EGCG) + folic acid (FA) + vitamin B12 (B12) + hyaluronic acid (HA) on HPV-positive cervical cancer cells (HeLa). RESULTS: The association of EGCG + FA + B12 + HA induced a significant increase of apoptosis and p53 gene expression with a concomitant decrease of E6/E7 gene expression, a marker of HPV infection. CONCLUSIONS: This study provides for the first-time evidence on the potential additive activity of EGCG + FA + B12 + HA in counteracting HPV infection, by increasing apoptosis and p53 expression in HPV-infected cervical HeLa cells.


Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Células HeLa , Proteína p53 Supresora de Tumor/genética , Ácido Hialurónico/farmacología , Neoplasias del Cuello Uterino/patología , Vitamina B 12/farmacología , Ácido Fólico/farmacología , Apoptosis
19.
Microbiome ; 11(1): 135, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37322528

RESUMEN

BACKGROUND: Pathogen infections seriously affect host health, and the use of antibiotics increases the risk of the emergence of drug-resistant bacteria and also increases environmental and health safety risks. Probiotics have received much attention for their excellent ability to prevent pathogen infections. Particularly, explaining mechanism of action of probiotics against pathogen infections is important for more efficient and rational use of probiotics and the maintenance of host health. RESULTS: Here, we describe the impacts of probiotic on host resistance to pathogen infections. Our findings revealed that (I) the protective effect of oral supplementation with B. velezensis against Aeromonas hydrophila infection was dependent on gut microbiota, specially the anaerobic indigenous gut microbe Cetobacterium; (II) Cetobacterium was a sensor of health, especially for fish infected with pathogenic bacteria; (III) the genome resolved the ability of Cetobacterium somerae CS2105-BJ to synthesize vitamin B12 de novo, while in vivo and in vitro metabolism assays also showed the ability of Cetobacterium somerae CS2105-BJ to produce vitamin B12; (IV) the addition of vitamin B12 significantly altered the gut redox status and the gut microbiome structure and function, and then improved the stability of the gut microbial ecological network, and enhanced the gut barrier tight junctions to prevent the pathogen infection. CONCLUSION: Collectively, this study found that the effect of probiotics in enhancing host resistance to pathogen infections depended on function of B12 produced by an anaerobic indigenous gut microbe, Cetobacterium. Furthermore, as a gut microbial regulator, B12 exhibited the ability to strengthen the interactions within gut microbiota and gut barrier tight junctions, thereby improving host resistance against pathogen infection. Video Abstract.


Asunto(s)
Microbioma Gastrointestinal , Probióticos , Animales , Vitamina B 12/farmacología , Probióticos/farmacología , Vitaminas
20.
Int J Mol Sci ; 24(12)2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37372992

RESUMEN

Vitamin B9 (folate)/B12 (cobalamin) deficiency is known to induce brain structural and/or functional retardations. In many countries, folate supplementation, targeting the most severe outcomes such as neural tube defects, is discontinued after the first trimester. However, adverse effects may occur after birth because of some mild misregulations. Various hormonal receptors were shown to be deregulated in brain tissue under these conditions. The glucocorticoid receptor (GR) is particularly sensitive to epigenetic regulation and post-translational modifications. In a mother-offspring rat model of vitamin B9/B12 deficiency, we investigated whether a prolonged folate supplementation could restore the GR signaling in the hypothalamus. Our data showed that a deficiency of folate and vitamin B12 during the in-utero and early postnatal periods was associated with reduced GR expression in the hypothalamus. We also described for the first time a novel post-translational modification of GR that impaired ligand binding and GR activation, leading to decrease expression of one of the GR targets in the hypothalamus, AgRP. Moreover, this brain-impaired GR signaling pathway was associated with behavioral perturbations during offspring growth. Importantly, perinatal and postnatal supplementation with folic acid helped restore GR mRNA levels and activity in hypothalamus cells and improved behavioral deficits.


Asunto(s)
Ácido Fólico , Deficiencia de Vitamina B 12 , Embarazo , Femenino , Animales , Ratas , Ácido Fólico/farmacología , Receptores de Glucocorticoides/genética , Glucocorticoides , Epigénesis Genética , Suplementos Dietéticos , Vitamina B 12/farmacología , Hipotálamo
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