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1.
Food Chem ; 368: 130768, 2022 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-34392120

RESUMEN

Apoptosis plays a critical role in sea cucumber autolysis. To investigate the ultraviolet (UV)-induced apoptosis, sea cucumbers with and without injection of BAPTA-AM (cytosolic calcium chelator) were exposed to UV (15 W/m2) for 30 min. The results showed that UV irradiation caused several changes in sea cucumber coelomocytes, including calcium imbalance, abnormal morphology of endoplasmic reticulum, upregulation of pro-apoptotic proteins CRT, CHOP, and caspases 9 and 3, and downregulation of anti-apoptotic protein Bcl-2. A comparison between the two groups showed that injection of the calcium chelator into sea cucumbers helped maintain coelomocyte intracellular calcium homeostasis and suppressed other abnormal changes caused by ER stress, indicating apoptosis in sea cucumbers is mediated by calcium imbalance and follows the activation of the ER stress pathway. Therefore, this study broadens understanding of the apoptotic mechanism involved in sea cucumber autolysis, which is helpful in developing preservative agents for sea cucumbers.


Asunto(s)
Pepinos de Mar , Stichopus , Animales , Autólisis , Calcio , Homeostasis
2.
Nat Commun ; 12(1): 5764, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34599187

RESUMEN

Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface protein normally expressed on neutrophil, is specifically expressed on Fate-1 TI Treg cells in several solid cancer types, but not on other TI or peripheral Treg cells. Mechanistically, blocking CD177 reduces the suppressive activity of Treg cells in vitro, while Treg-specific deletion of Cd177 leads to decreased tumor growth and reduced TI Treg frequency in mice. Our results thus uncover a functional CD177+ TI Treg population that may serve as a target for TI Treg-specific immunotherapy.


Asunto(s)
Proteínas Ligadas a GPI/metabolismo , Homeostasis , Isoantígenos/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Receptores de Superficie Celular/metabolismo , Linfocitos T Reguladores/metabolismo , Animales , Secuencia de Bases , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Proteínas Ligadas a GPI/deficiencia , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Ratones Noqueados , Pronóstico , Receptores de Superficie Celular/deficiencia , Análisis de la Célula Individual , Transcripción Genética
3.
Front Cell Infect Microbiol ; 11: 696554, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34595127

RESUMEN

The circadian clock regulates numerous key physiological processes and maintains cellular, tissue, and systemic homeostasis. Disruption of circadian clock machinery influences key activities involved in immune response and brain function. Moreover, Immune activation has been closely linked to neurodegeneration. Here, we review the molecular clock machinery and the diurnal variation of immune activity. We summarize the circadian control of immunity in both central and peripheral immune cells, as well as the circadian regulation of brain cells that are implicated in neurodegeneration. We explore the important role of systemic inflammation on neurodegeneration. The circadian clock modulates cellular metabolism, which could be a mechanism underlying circadian control. We also discuss the circadian interventions implicated in inflammation and neurodegeneration. Targeting circadian clocks could be a potential strategy for the prevention and treatment of inflammation and neurodegenerative diseases.


Asunto(s)
Relojes Circadianos , Encéfalo , Ritmo Circadiano , Homeostasis , Humanos , Inflamación
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1380-1386, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34627414

RESUMEN

OBJECTIVE: To investigate the effect of autophagy to the ferroptosis in acute lymphocytic leukemia (ALL) cells and its mechanism. METHODS: ALL cell lines (including Reh, Jurkat and CCRF-CEM) were selected. The cell viability was detected by MTS assay and trypan blue staining was used to evaluate the death of the cell. The expression of autophagy related protein (including p62, LC3I/II) and Ferritin in ALL cells were detected by Western blot. The alteration of labile iron pool (LIP) in ALL cells was evaluated by flow cytometry. RESULTS: Reh cells showed sensitivity to ferroptosis activator Erastin, while Jurkat and CCRF-CEM cells showed resistant. Autophagy activator rapamycin could promote the sensitivity of Jurkat and CCRF-CEM cells to Erastin, and the ferroptosis of the cells (P<0.001). Autophagy inhibitor chloroquine could reduce the sensitivity of Reh cells to Erastin and resist the ferroptosis of the cells (P<0.001). The expression of Ferritin could be down-regulated after autophagy was activated in Jurkat and CCRF-CEM cells (P<0.05), while the level of LIP was significantly increased (P<0.05). Inhibiting the autophgy in Reh cells could up-regulate the expression of Ferritin (P<0.01),while decrease the level of LIP (P<0.001). CONCLUSION: The iron homeostasis in cells could be regulated by autophagy through affecting Ferritin expression and LIP level. Autophagy can alter sensitivity of ALL cells to ferroptosis activator Erastin, which suggestes that combining autophagy regulator with ferroptosis activator may be a new strategy for the treatment of chemotherapy-resistant ALL.


Asunto(s)
Ferroptosis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Autofagia , Homeostasis , Humanos , Hierro , Especies Reactivas de Oxígeno
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1623-1630, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34627451

RESUMEN

OBJECTIVE: To investigate the effect of lysosomal-associated protein transmembrane-4 Beta(Laptm4b) deletion on hematopoietic stem/progenitor cells (HSPCs) homeostasis in mice. METHODS: The hematopoietic system specific Laptm4b-deficient mice were constructed. The number and proportion of HSPCs (LSK, LT, ST, MPP, etc) in Laptm4b-deficient mice were analyzed by flow cytometry. Single SLAM-HSC cell was sorted by flow sorter and cultured in vitro to measure the effect of Laptm4b deletion on the colony forming ability of hematopoietic stem cells (HSCs). The effect of Laptm4b-deficient on the reconstitution ability of HSCs in mice was detected by competitive transplantation experiment of SLAM-HSC cells. RESULTS: Laptm4b deficiency could moderately upregulate the proportion of T cells in the peripheral blood of the mice, but showed no significant effect on the proportion and number of HSPCs. Laptm4b deletion showed no effect on the reconstruction ability of HSCs after competitive transplantation, but it could inhibit the colony formation of HSCs in vitro. CONCLUSION: LAPTM4B may play a role in HSCs under the proliferation stress. Laptm4b-deficient in mice hematopoietic system showed no significant effect on the HSPCs homeostasis maintenance and reconstruction ability.


Asunto(s)
Células Madre Hematopoyéticas , Factores de Transcripción , Animales , Proliferación Celular , Citometría de Flujo , Homeostasis , Ratones
6.
Adv Physiol Educ ; 45(4): 812-828, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34633855

RESUMEN

Homeostasis is a core concept in systems physiology that future clinicians and biomedical professionals will apply in their careers. Despite this, many students struggle to transfer the principles governing homeostasis to concrete examples. Precourse assessments conducted on 72 undergraduate biology students enrolled in an introductory systems physiology course at the University of Belgrade during the February-May semester of 2021 revealed that students had a vague, fragmentary understanding of homeostasis and its related concepts that was often conflated with topics touched on during their previous coursework. We formalized and implemented an approach to teaching homeostasis that focused heavily on consistent reinforcement of physiological reflex patterns throughout the course. To that end, we employed a variety of activities aimed at getting students to view organ system integration holistically. After the semester, postcourse assessment demonstrated that students were better able to provide concrete examples of organ system contributions to homeostasis and were more adept at applying basic principles to novel physiological scenarios. Comparison of final grades with previous semesters revealed that students outperformed their peers who had taken the course previously. In this article, we summarize the findings of pre- and postcourse assessments, describe the general approach we took to teaching homeostasis as well as the specific techniques used in the classroom, and compare student performance with previous semesters.


Asunto(s)
Evaluación Educacional , Estudiantes , Homeostasis , Humanos
7.
Nat Commun ; 12(1): 5323, 2021 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-34493722

RESUMEN

The role of intestine clock in energy homeostasis remains elusive. Here we show that mice with Bmal1 specifically deleted in the intestine (Bmal1iKO mice) have a normal phenotype on a chow diet. However, on a high-fat diet (HFD), Bmal1iKO mice are protected against development of obesity and related abnormalities such as hyperlipidemia and fatty livers. These metabolic phenotypes are attributed to impaired lipid resynthesis in the intestine and reduced fat secretion. Consistently, wild-type mice fed a HFD during nighttime (with a lower BMAL1 expression) show alleviated obesity compared to mice fed ad libitum. Mechanistic studies uncover that BMAL1 transactivates the Dgat2 gene (encoding the triacylglycerol synthesis enzyme DGAT2) via direct binding to an E-box in the promoter, thereby promoting dietary fat absorption. Supporting these findings, intestinal deficiency of Rev-erbα, a known BMAL1 repressor, enhances dietary fat absorption and exacerbates HFD-induced obesity and comorbidities. Moreover, small-molecule targeting of REV-ERBα/BMAL1 by SR9009 ameliorates HFD-induced obesity in mice. Altogether, intestine clock functions as an accelerator in dietary fat absorption and targeting intestinal BMAL1 may be a promising approach for management of metabolic diseases induced by excess fat intake.


Asunto(s)
Factores de Transcripción ARNTL/genética , Ritmo Circadiano/genética , Diacilglicerol O-Acetiltransferasa/genética , Hígado Graso/genética , Hiperlipidemias/genética , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Obesidad/genética , Factores de Transcripción ARNTL/deficiencia , Animales , Diacilglicerol O-Acetiltransferasa/metabolismo , Dieta Alta en Grasa/efectos adversos , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/metabolismo , Hígado Graso/etiología , Hígado Graso/metabolismo , Hígado Graso/prevención & control , Regulación de la Expresión Génica , Homeostasis/efectos de los fármacos , Homeostasis/genética , Hiperlipidemias/etiología , Hiperlipidemias/metabolismo , Hiperlipidemias/prevención & control , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/antagonistas & inhibidores , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/metabolismo , Obesidad/etiología , Obesidad/metabolismo , Obesidad/prevención & control , Regiones Promotoras Genéticas , Unión Proteica , Pirrolidinas/farmacología , Transducción de Señal , Tiofenos/farmacología , Triglicéridos/biosíntesis
8.
Cells ; 10(9)2021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34571911

RESUMEN

The rising prevalence of diabetes is threatening global health. It is known not only for the occurrence of severe complications but also for the SARS-Cov-2 pandemic, which shows that it exacerbates susceptibility to infections. Current therapies focus on artificially maintaining insulin homeostasis, and a durable cure has not yet been achieved. We demonstrate that our set of small molecule inhibitors of DYRK1A kinase potently promotes ß-cell proliferation, enhances long-term insulin secretion, and balances glucagon level in the organoid model of the human islets. Comparable activity is seen in INS-1E and MIN6 cells, in isolated mice islets, and human iPSC-derived ß-cells. Our compounds exert a significantly more pronounced effect compared to harmine, the best-documented molecule enhancing ß-cell proliferation. Using a body-like environment of the organoid, we provide a proof-of-concept that small-molecule-induced human ß-cell proliferation via DYRK1A inhibition is achievable, which lends a considerable promise for regenerative medicine in T1DM and T2DM treatment.


Asunto(s)
Homeostasis , Células Secretoras de Insulina/citología , Células Secretoras de Insulina/enzimología , Insulina/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Genes Reporteros , Harmina/farmacología , Homeostasis/efectos de los fármacos , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Cinética , Masculino , Ratones , Modelos Biológicos , Factores de Transcripción NFATC/metabolismo , Organoides/efectos de los fármacos , Organoides/metabolismo , Inhibidores de Proteínas Quinasas/química , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Ratas , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/metabolismo
9.
Chem Biol Interact ; 348: 109649, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34516972

RESUMEN

Cadmium (Cd) exposure induced lipid metabolic disorder with changes in lipid composition, as well as triglyceride (TG) levels. Liver is the main organ maintaining body TG level and previous studies suggested that Cd exposure might increase TG synthesis but reduce TG uptake in liver. However, the effects of Cd exposure on TG secretion from liver and underlying mechanism are still unclear. In the present study, the data revealed that Cd exposure increased TG levels in the HepG2 cells and the cultured medium by increasing the expression of microsomal triglyceride transfer protein (MTTP), which was abrogated by siRNA knockdown of MTTP. MTTP was synergistically accumulated after Cd exposure or treated with proteasome inhibitor MG132 and lysosome inhibitor chloroquine (CQ), which suggested the Cd increased MTTP protein stability by inhibiting both the proteasome and the lysosomal protein degradation pathways. In addition, our results demonstrated that Cd exposure inhibited the lysosomal acidic degradation pathway through disrupting endoplastic reticulum (ER) Ca2+ homeostasis. Cd-induced MTTP protein and TG levels were significantly reduced by pretreatments of BAPTA/AM chelation of intracellular Ca2+, 2-APB inhibition of ER Ca2+ release channel inositol 1,4,5-trisphosphate receptor (IP3R) and CDN1163 activation of ER Ca2+ reuptake pump sarcoplasmic reticulum Ca2+-ATPase (SERCA). These results suggest that Cd-induced ER Ca2+ release impaired the lysosomal acidity, which associated with MTTP protein accumulation and contributed to increased TG levels.


Asunto(s)
Cadmio/farmacología , Proteínas Portadoras/metabolismo , Retículo Endoplásmico/metabolismo , Homeostasis/efectos de los fármacos , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Triglicéridos/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Células Hep G2 , Humanos , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo
10.
Planta ; 254(4): 65, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34487248

RESUMEN

MAIN CONCLUSION: Enhanced levels of indole-3-acetic and raised auxin to cytokinin ratios in the stem base contribute to the positive acropetal gradient in rooting capacity of leafy single-node stem cuttings of rose. Cuttings excised from different nodal positions in stock plants can differ in subsequent adventitious root formation. We investigated the involvement of the auxin-cytokinin balance in position-affected rooting of Rosa hybrida. Leafy single-node stem cuttings of two rose cultivars were excised from top versus bottom positions. Concentrations of IAA and cytokinins were monitored in the bud region and the stem base during 8 days after planting using chromatography-MS/MS technology. The effects of nodal position and external supply of indole-butyric acid on rooting were analyzed. Most cytokinins increased particularly in the bud region and peaked at day two before the bud break was recorded. IAA increased in both tissues between day one and day eight. Top versus bottom cuttings revealed higher levels of isopentenyladenosine (IPR) in both tissues as well as higher concentrations of IAA and a higher ratio of IAA to cytokinins particularly in the stem base. The dynamic of hormones and correlation analysis indicated that the higher IPR contributed to the enhanced IAA in the bud region which served as auxin source for the auxin homeostasis in the stem base, where IAA determined the auxin-cytokinin balance. Bottom versus top cuttings produced lower numbers and lengths of roots, whereas this deficit was counterbalanced by auxin application. Further considering other studies of rose, it is concluded that cytokinin-, sucrose- and zinc-dependent auxin biosynthesis in the outgrowing buds is an important factor that contributes to the enhanced IAA levels and auxin/cytokinin ratios in the stem base of apical cuttings, promoting root induction.


Asunto(s)
Citocininas , Rosa , Homeostasis , Ácidos Indolacéticos , Raíces de Plantas , Espectrometría de Masas en Tándem
11.
Zh Nevrol Psikhiatr Im S S Korsakova ; 121(8. Vyp. 2): 30-34, 2021.
Artículo en Ruso | MEDLINE | ID: mdl-34553578

RESUMEN

OBJECTIVE: To study the conjugate dynamics of vascular endothelial growth factor (VEGF) and the components of metal-ligand homeostasis in the development of ischemic stroke. MATERIAL AND METHODS: The main group included patients with ischemic stroke (n=158). The comparison group consisted of healthy volunteers (n=150). The concentration of VEGF (pg/ml) in the blood serum was determined by ELISA and concentrations of Mg, Cu, Mn, Se, Zn and Fe (mcg/ml) by inductively coupled argon plasma mass spectrometry. Data analysis was carried out using the Statistica 10 application software package and the optimal reliable partitioning (SDR) method, which is part of the Date mining group of data mining methods. RESULTS: A significant increase in the concentrations of VEGF and trace elements Mg, Mn, Cu, Zn, and Se in the blood serum of patients with ischemic stroke was revealed. A significant relationship between the concentration of VEGF and the concentrations of Cu and Mn in the blood serum of patients with ischemic stroke was shown. CONCLUSION: The dynamics of VEGF and the concentrations of trace elements in the development of the ischemic process contribute to the solution of therapeutic and prognostic problems in clinical conditions.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Oligoelementos , Homeostasis , Humanos , Ligandos , Factor A de Crecimiento Endotelial Vascular
12.
Braz J Biol ; 83: e250179, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34524376

RESUMEN

Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.


Asunto(s)
Diabetes Mellitus , Resistencia a la Insulina , Glucosa , Glucógeno Sintasa Quinasa 3 , Homeostasis , Humanos
14.
Int J Clin Pract ; 75(11): e14838, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34519144

RESUMEN

OBJECTIVE: We aimed to investigate the effects of hypotensive anaesthesia on oxidative stress with serum thiol/disulphide balance in patients undergoing elective septoplasty procedures under general anaesthesia. METHODS: Seventy-two patients between the ages of 18-60, with a physical condition I -II, according to the American Society of Anesthesiologists, were included in this prospective observational study. Septoplasty was chosen for standard surgical stress. According to the maintenance of anaesthesia, patients were divided into the groups as Hypotensive Anaesthesia (n = 40) and Normotensive Anaesthesia (n = 32). Serum thiol/disulphide levels were measured by the method developed by Erel & Neselioglu. RESULTS: The native thiol and total thiol values of both groups measured at the 60th min intraoperatively were significantly lower than the preoperative values (both P < .01). Intraoperatively, at the 60th min, there was no significant difference in terms of post-native thiol and post-total thiol levels between hypotensive and normotensive anaesthesia groups (P = .68 and .81, respectively). Age >40 years and female gender were found to have a significant effect on dynamic oxidative stress (P = .002 and .001, respectively). CONCLUSION: This pilot study has found that hypotensive anaesthesia had no adverse effect on dynamic thiol/disulphide balance in elective surgeries.


Asunto(s)
Anestesia , Disulfuros , Adolescente , Adulto , Femenino , Homeostasis , Humanos , Persona de Mediana Edad , Estrés Oxidativo , Proyectos Piloto , Compuestos de Sulfhidrilo , Adulto Joven
15.
Int J Clin Pract ; 75(11): e14872, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34525247

RESUMEN

AIMS: In this study, we aimed to investigate the anti-inflammatory and antioxidant effects of intravenous ibuprofen by using the C-reactive protein level and thiol/disulfide homeostasis as the oxidative stress marker. MATERIALS AND METHODS: This study was conducted on 70 patients aged between 30 and 65 who were scheduled for elective laparoscopic hysterectomy. The patients were divided into two groups to receive either pre-emptive 800mg of intravenous ibuprofen plus 1000 mg of intravenous paracetamol (Group IP) or only 1000 mg of intravenous paracetamol as a control group (Group P). The blood samples for thiol/disulfide homeostasis were collected as follows: before induction of anesthesia (T0), before pneumoperitoneum (T1), following postdeflation and discontinuation of anesthesia (T2), and postoperative 24th hour (T3). Simultaneous blood samples for C-reactive protein (CRP) were also collected. The pre- and postoperative urea, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were measured. RESULTS: A total of 69 patients were included in the study. The patient's characteristics and intraoperative variables were comparable between groups (P > .05). The number of patients requiring rescue analgesia, the total amount of analgesic used, Visual Analog Scale (VAS) scores, and postoperative side effects were significantly lower in Group IP (P < .001). The decrease in native and total thiol levels at T1, T2, and T3 measurement points was significant in Group IP (P < .001). In both groups, the comparison to baseline values demonstrated no significant changes in terms of disulfide level (P > .05). The simultaneous CRP levels indicated a significant increase at the postoperative 24 hour in both groups (P < .001). The difference between groups was insignificant (P > .05). There was a significant increase in urea and creatinine levels in patients of Group IP (P < .05). CONCLUSION: The pre-emptive administration of ibuprofen provided effective pain control after gynecologic laparoscopy. However, ibuprofen changed the thiol/disulfide homeostasis in favor of oxidation and had no beneficial effect in surgically induced oxidative stress.


Asunto(s)
Ibuprofeno , Laparoscopía , Adulto , Anciano , Proteína C-Reactiva , Disulfuros , Femenino , Homeostasis , Humanos , Inflamación , Persona de Mediana Edad , Estrés Oxidativo , Compuestos de Sulfhidrilo
16.
Mol Cell ; 81(18): 3677-3690, 2021 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-34547233

RESUMEN

The evolution of AMPK and its homologs enabled exquisite responsivity and control of cellular energetic homeostasis. Recent work has been critical in establishing the mechanisms that determine AMPK activity, novel targets of AMPK action, and the distribution of AMPK-mediated control networks across the cellular landscape. The role of AMPK as a hub of metabolic control has led to intense interest in pharmacologic activation as a therapeutic avenue for a number of disease states, including obesity, diabetes, and cancer. As such, critical work on the compartmentalization of AMPK, its downstream targets, and the systems it influences has progressed in recent years. The variegated distribution of AMPK-mediated control of metabolic homeostasis has revealed key insights into AMPK in normal biology and future directions for AMPK-based therapeutic strategies.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Animales , Citoplasma/metabolismo , Metabolismo Energético , Homeostasis , Humanos , Mitocondrias/metabolismo , Dominios Proteicos , Transducción de Señal , Relación Estructura-Actividad
17.
Nat Commun ; 12(1): 5416, 2021 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-34518544

RESUMEN

Hypoxia is the most prominent feature in human solid tumors and induces activation of hypoxia-inducible factors and their downstream genes to promote cancer progression. However, whether and how hypoxia regulates overall mRNA homeostasis is unclear. Here we show that hypoxia inhibits global-mRNA decay in cancer cells. Mechanistically, hypoxia induces the interaction of AGO2 with LUBAC, the linear ubiquitin chain assembly complex, which co-localizes with miRNA-induced silencing complex and in turn catalyzes AGO2 occurring Met1-linked linear ubiquitination (M1-Ubi). A series of biochemical experiments reveal that M1-Ubi of AGO2 restrains miRNA-mediated gene silencing. Moreover, combination analyses of the AGO2-associated mRNA transcriptome by RIP-Seq and the mRNA transcriptome by RNA-Seq confirm that AGO2 M1-Ubi interferes miRNA-targeted mRNA recruiting to AGO2, and thereby facilitates accumulation of global mRNAs. By this mechanism, short-term hypoxia may protect overall mRNAs and enhances stress tolerance, whereas long-term hypoxia in tumor cells results in seriously changing the entire gene expression profile to drive cell malignant evolution.


Asunto(s)
Proteínas Argonauta/genética , Regulación Neoplásica de la Expresión Génica , Homeostasis/genética , Metionina/genética , ARN Mensajero/genética , Ubiquitinación , Células A549 , Proteínas Argonauta/metabolismo , Hipoxia de la Célula , Línea Celular Tumoral , Silenciador del Gen , Células HEK293 , Células HeLa , Humanos , Hipoxia , Metionina/metabolismo , MicroARNs/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Células PC-3 , Estabilidad del ARN/genética , ARN Mensajero/metabolismo
18.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34576130

RESUMEN

Several studies have sought new therapies for obesity and liver diseases. This study investigated the effect of the trypsin inhibitor isolated from tamarind seeds (TTI), nanoencapsulated in chitosan and whey protein isolate (ECW), on the liver health status of the Wistar rats fed with a high glycemic index (HGLI) diet. The nanoformulations without TTI (CW) and ECW were obtained by nanoprecipitation technique, physically and chemically characterized, and then administered to the animals. The adult male Wistar rats (n = 20) were allocated to four groups: HGLI diet + water; standard diet + water; HGLI diet + ECW (12.5 mg/kg); and HGLI diet + CW (10.0 mg/kg), 1 mL per gagave, for ten days. They were evaluated using biochemical and hematological parameters, Fibrosis-4 Index for Liver Fibrosis (FIB-4), AST to Platelet Ratio Index (APRI) scores, and liver morphology. Both nanoparticles presented spherical shape, smooth surface, and nanometric size [120.7 nm (ECW) and 136.4 nm (CW)]. In animals, ECW reduced (p < 0.05) blood glucose (17%), glutamic oxalacetic transaminase (39%), and alkaline phosphatase (24%). Besides, ECW reduced (p < 0.05) APRI and FIB-4 scores and presented a better aspect of hepatic morphology. ECW promoted benefits over a liver injury caused by the HGLI diet.


Asunto(s)
Quitosano/química , Dieta , Índice Glucémico , Hígado/lesiones , Nanopartículas/química , Tamarindus/química , Inhibidores de Tripsina/farmacología , Proteína de Suero de Leche/química , Animales , Glucemia/metabolismo , Ayuno/sangre , Homeostasis , Insulina/sangre , Resistencia a la Insulina , Riñón/fisiopatología , Hígado/efectos de los fármacos , Hígado/patología , Hígado/fisiopatología , Masculino , Nanopartículas/ultraestructura , Ratas Wistar , Valores de Referencia
19.
Mol Cell ; 81(18): 3691-3707, 2021 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-34547234

RESUMEN

Redox reactions are intrinsically linked to energy metabolism. Therefore, redox processes are indispensable for organismal physiology and life itself. The term reactive oxygen species (ROS) describes a set of distinct molecular oxygen derivatives produced during normal aerobic metabolism. Multiple ROS-generating and ROS-eliminating systems actively maintain the intracellular redox state, which serves to mediate redox signaling and regulate cellular functions. ROS, in particular hydrogen peroxide (H2O2), are able to reversibly oxidize critical, redox-sensitive cysteine residues on target proteins. These oxidative post-translational modifications (PTMs) can control the biological activity of numerous enzymes and transcription factors (TFs), as well as their cellular localization or interactions with binding partners. In this review, we describe the diverse roles of redox regulation in the context of physiological cellular metabolism and provide insights into the pathophysiology of diseases when redox homeostasis is dysregulated.


Asunto(s)
Metabolismo Energético/fisiología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiología , Animales , Cisteína/metabolismo , Homeostasis , Humanos , Peróxido de Hidrógeno/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Procesamiento Proteico-Postraduccional/fisiología
20.
Mol Cell ; 81(18): 3708-3730, 2021 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-34547235

RESUMEN

Lipids play crucial roles in signal transduction, contribute to the structural integrity of cellular membranes, and regulate energy metabolism. Questions remain as to which lipid species maintain metabolic homeostasis and which disrupt essential cellular functions, leading to metabolic disorders. Here, we discuss recent advances in understanding lipid metabolism with a focus on catabolism, synthesis, and signaling. Technical advances, including functional genomics, metabolomics, lipidomics, lipid-protein interaction maps, and advances in mass spectrometry, have uncovered new ways to prioritize molecular mechanisms mediating lipid function. By reviewing what is known about the distinct effects of specific lipid species in physiological pathways, we provide a framework for understanding newly identified targets regulating lipid homeostasis with implications for ameliorating metabolic diseases.


Asunto(s)
Metabolismo de los Lípidos/fisiología , Enfermedades Metabólicas/metabolismo , Transducción de Señal/fisiología , Animales , Cromatina/metabolismo , Enfermedad , Metabolismo Energético/fisiología , Salud , Homeostasis/fisiología , Humanos , Inmunidad/fisiología , Lipidómica/métodos , Lípidos/fisiología , Enfermedades Metabólicas/fisiopatología , Metabolómica/métodos , Microbiota/fisiología
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