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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(1): 54-57, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35048600

RESUMO

The proper development and the homeostasis maintenance of bones are important prerequisites for the normal functioning of the human body. Bone developmental deformities or homeostasis disorders, such as Kashin-Beck disease, craniosynostosis, cleft palate and osteoarthritis, severely affect the life of patients, causing significant stress to the family and the society. Fibroblast growth factor 8 (FGF8) plays multiple functions through the course of the life of organisms. Abnormal expression of FGF8 may cause disorders of bone homeostasis and developmental abnormalities of bones. More and more studies have found that FGF8 may play an important role in bone development and may become a potential therapeutic target. Herein, we reviewed the role of FGF8 in a variety of skeletal abnormalities, intending to provide new perspectives for the prevention and treatment of related diseases in the future.


Assuntos
Desenvolvimento Ósseo , Fatores de Crescimento de Fibroblastos , Osso e Ossos/metabolismo , Fator 8 de Crescimento de Fibroblasto , Fatores de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica no Desenvolvimento , Homeostase , Humanos
2.
Handb Clin Neurol ; 184: 53-72, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35034758

RESUMO

Sleep homeostasis is a complex neurobiologic phenomenon involving a number of molecular pathways, neurotransmitter release, synaptic activity, and factors modulating neural networks. Sleep plasticity allows for homeostatic optimization of neural networks and the replay-based consolidation of specific circuits, especially important for cognition, behavior, and information processing. Furthermore, research is currently moving from an essentially brain-focused to a more comprehensive view involving other systems, such as the immune system, hormonal status, and metabolic pathways. When dysfunctional, these systems contribute to sleep loss and fragmentation as well as to sleep need. In this chapter, the implications of neural plasticity and sleep homeostasis for the diagnosis and treatment of some major sleep disorders, such as insomnia and sleep deprivation, obstructive sleep apnea syndrome, restless legs syndrome, REM sleep behavior disorder, and narcolepsy are discussed in detail with their therapeutical implications. This chapter highlights that sleep is necessary for the maintenance of an optimal brain function and is sensitive to both genetic background and environmental enrichment. Even in pathologic conditions, sleep acts as a resilient plastic state that consolidates prior information and prioritizes network activity for efficient brain functioning.


Assuntos
Narcolepsia , Síndrome das Pernas Inquietas , Transtornos do Sono-Vigília , Homeostase , Humanos , Plasticidade Neuronal , Sono
3.
Soft Matter ; 18(3): 675-679, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34985470

RESUMO

Many cell-types that reside within load bearing tissues appear to exhibit mechanical homeostasis, that is, a tendency to regulate particular mechanical quantities near a preferred value, often called a set-point. It is suggested here that assessing potential mechanical homeostasis requires careful attention to derivations and definitions, that is, appropriate solutions to the initial-boundary value problems that define the biophysical situation of interest and appropriate definitions of what is meant by homeostasis. Noting that this term was coined carefully, with homeo meaning "similar to" in contrast to homo meaning "the same as", one must be careful not only to identify the key mechano-regulated quantity (e.g., a stress rather than a flow or a force) but also the tolerance that defines the range of regulation, noting too that the specific target value of that variable may differ from region to region within the body while yet being regulated locally. Herein, we present a few examples to highlight specific derivations and definitions of importance when studying mechanical homeostasis across scales.


Assuntos
Homeostase
4.
Soft Matter ; 18(3): 680-682, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34985478

RESUMO

Drs Humphrey and Cyron wrote a commentary regarding our review article entitled "Tensional homeostasis at different length scales" that was published in Soft Matter, 2020, 16, 6946-6963. These authors brought up some valid concerns to which we would like to respond. Their first concern is related to our remark regarding equations that we used to describe homeostasis in blood vessels, where we stated that those equations were limited only to linearly elastic materials. We were wrong, and we agree with the authors that these equations hold for all cylindrical vessels regardless of their material properties. Their second concern is related to tensional homeostasis at the subcellular level. Drs Humphrey and Cyron disagree with our substantiated claim that tensional homeostasis breaks down at the level of focal adhesions (FAs) of a living cell. In our reply, we provided several pieces of evidence that demonstrate that tensional homeostasis depends upon FA size, FA maturity and FA force dynamics and thus, tensional homeostasis cannot hold in all FAs across a cell. In summary, we are grateful for the opportunity to reply to the commentary of Drs Humphrey and Cyron. Moreover, we are excited that this topic has become an important focus in the biomechanics and mechanobiology communities, and we feel strongly that critical feedback is necessary to move this field forward.


Assuntos
Adesões Focais , Fenômenos Mecânicos , Fenômenos Biomecânicos , Homeostase
5.
In Vivo ; 36(1): 161-169, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972711

RESUMO

BACKGROUND/AIM: This study aimed to investigate the process of homeostatic restoration in the tracheal mucosa (TM) after thyroid surgery. MATERIALS AND METHODS: Fifty-four rats were divided into normal controls (NC) and three experimental groups: (i) flap elevation (FE), (ii) thyroid exposure (TE), and (iii) thyroid isthmusectomy (TI). Expression of mRNA and proteins of key factors regulating homeostasis were evaluated in the TM obtained 3, 7, and 21 days after thyroid surgery. RESULTS: Increased mRNA expression of transforming growth factor-ß1 (TGF-ß1), hypoxia-inducible factor-1α (HIF-1α), and matrix metalloproteinase-9 (MMP-9) were observed 21 days after thyroid surgery in all experimental groups compared to that of NC group. CONCLUSION: Thyroid surgery leads to an actual increase of TGF-ß1, HIF-1α, and MMP-9 expression in the TM. This increased expression of key regulators of homeostatic restoration in the TM lasts for a considerable period of time after surgery, especially if the extent of surgery increased.


Assuntos
Glândula Tireoide , Fator de Crescimento Transformador beta1 , Animais , Homeostase , Membrana Mucosa , RNA Mensageiro/genética , Ratos , Glândula Tireoide/cirurgia , Fator de Crescimento Transformador beta1/genética
6.
Gene ; 809: 146017, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34655725

RESUMO

Flavonoids and lignin consist of a large number of secondarymetabolites which are derived from the phenylpropanoid pathway, and they act as a significant role in plant growth, development, and stress response. However, few reports have documented that how different subbranches of phenylpropanoid metablolic pathway mutually interact. In Arabidopsis, AtCPC (AtCAPRICE) is known to play a negative role in anthocyanin accumulation. Nonetheless, whether AtCPC could control the biosynthesis of lignin is largely unknown. Additionally, whether the RrFLS and RrANR, flavonol synthase and anthocyanidin reductase, from Rosa rugosa regulate different branches of phenylpropanoid pathway is unclear. Here, we performed a series of transgenic experiments with short life cycle tobacco and RNA-Seq analysis. Finally, a series of assays related to biological, physiological, and phenotypic characteristics were undertaken. Our results indicated that ectopic expression of AtCPC in tobacco not only decreased the flavonoid compound accumulation, but also up-regulated several lignin biosynthetic genes, and significantly increased the accumulation of lignin. Our results also revealed that although they respectively improved the flavonol and proanthocyanidin contents, the overexpression of RrFLS and RrANR plays positive roles in lignin biosynthesis in transgenic tobacco plants. Our findings provide a novel insight into the mechanism underlying homeostatic regulation of flavonoid and lignin biosynthesis in phenylpropanoid pathway of plants.


Assuntos
Flavonoides/biossíntese , Lignina/biossíntese , Tabaco/genética , Tabaco/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flavonoides/genética , Regulação da Expressão Gênica de Plantas , Homeostase , Lignina/genética , NADH NADPH Oxirredutases/genética , NADH NADPH Oxirredutases/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/metabolismo , Rosa/genética , Fatores de Transcrição/genética
7.
Biochim Biophys Acta Gen Subj ; 1866(1): 130017, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34624450

RESUMO

BACKGROUND: Autophagy, a highly conserved homeostatic mechanism, is essential for cell survival. The decline of autophagy function has been implicated in various diseases as well as aging. Although mitochondria play a key role in the autophagy process, whether mitochondrial-derived peptides are involved in this process has not been explored. METHODS: We developed a high through put screening method to identify potential autophagy inducers among mitochondrial-derived peptides. We used three different cell lines, mice, c.elegans, and a human cohort to validate the observation. RESULTS: Humanin, a mitochondrial-derived peptide, increases autophagy and maintains autophagy flux in several cell types. Humanin administration increases the expression of autophagy-related genes and lowers accumulation of harmful misfolded proteins in mice skeletal muscle, suggesting that humanin-induced autophagy potentially contributes to the improved skeletal function. Moreover, autophagy is a critical role in humanin-induced lifespan extension in C. elegans. CONCLUSIONS: Humanin is an autophagy inducer. GENERAL SIGNIFICANCE: This paper presents a significant, novel discovery regarding the role of the mitochondrial derived peptide humanin in autophagy regulation and as a possible therapeutic target for autophagy in various age-related diseases.


Assuntos
Autofagia/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Músculo Esquelético/metabolismo , Envelhecimento , Animais , Caenorhabditis elegans/metabolismo , Linhagem Celular , Sobrevivência Celular , Células HEK293 , Homeostase , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Longevidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Músculo Esquelético/fisiologia , Peptídeos/metabolismo
8.
FASEB J ; 36(1): e22062, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34918377

RESUMO

Mitochondrial dysfunction or loss of homeostasis is a central hallmark of many human diseases. Mitochondrial homeostasis is mediated by multiple quality control mechanisms including mitophagy, a form of selective autophagy that recycles terminally ill or dysfunctional mitochondria in order to preserve mitochondrial integrity. Our prior studies have shown that members of the insulin-like growth factor (IGF) family localize to the mitochondria and may play important roles in mediating mitochondrial health in the corneal epithelium, an integral tissue that is required for the maintenance of optical transparency and vision. Importantly, the IGF-binding protein-3, IGFBP-3, is secreted by corneal epithelial cells in response to stress and functions to mediate intracellular receptor trafficking in this cell type. In this study, we demonstrate a novel role for IGFBP-3 in mitochondrial homeostasis through regulation of the short isoform (s)BNIP3L/NIX mitophagy receptor in corneal epithelial cells and extend this finding to non-ocular epithelial cells. We further show that IGFBP-3-mediated control of mitochondrial homeostasis is associated with alterations in lamellar cristae morphology and mitochondrial dynamics. Interestingly, both loss and gain of function of IGFBP-3 drive an increase in mitochondrial respiration. This increase in respiration is associated with nuclear accumulation of IGFBP-3. Taken together, these findings support a novel role for IGFBP-3 as a key mediator of mitochondrial health in mucosal epithelia through the regulation of mitophagy and mitochondrial morphology.


Assuntos
Epitélio Corneano/metabolismo , Homeostase , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Mitocôndrias/metabolismo , Mitofagia , Linhagem Celular Transformada , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteínas de Membrana/metabolismo , Mitocôndrias/genética , Membrana Mucosa/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo
9.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34534278

RESUMO

Cross-talk between peripheral tissues is essential to ensure the coordination of nutrient intake with disposition during the feeding period, thereby preventing metabolic disease. This mini-review considers the interactions between the key peripheral tissues that constitute the metabolic clock, each of which is considered in a separate mini-review in this collation of articles published in Endocrinology in 2020 and 2021, by Martchenko et al (Circadian rhythms and the gastrointestinal tract: relationship to metabolism and gut hormones); Alvarez et al (The microbiome as a circadian coordinator of metabolism); Seshadri and Doucette (Circadian regulation of the pancreatic beta cell); McCommis et al (The importance of keeping time in the liver); Oosterman et al (The circadian clock, shift work, and tissue-specific insulin resistance); and Heyde et al (Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism). The use of positive- and negative-feedback signals, both hormonal and metabolic, between these tissues ensures that peripheral metabolic pathways are synchronized with the timing of food intake, thus optimizing nutrient disposition and preventing metabolic disease. Collectively, these articles highlight the critical role played by the circadian clock in maintaining metabolic homeostasis.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano , Comportamento Alimentar , Homeostase , Fígado/fisiologia , Adipócitos/citologia , Animais , Endocrinologia/métodos , Ingestão de Energia , Metabolismo Energético/fisiologia , Retroalimentação Fisiológica , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Intestinos/fisiologia , Ilhotas Pancreáticas/citologia , Mamíferos/fisiologia , Doenças Metabólicas/metabolismo , Microbiota , Modelos Biológicos , Células Musculares/citologia , Músculo Esquelético/fisiologia
10.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34669927

RESUMO

Thyroid hormones (TH) are essential for skeletal development and adult bone homeostasis. Their bioavailability is determined by specific transporter proteins at the cell surface. The TH-specific transporter monocarboxylate transporter 8 (MCT8) was recently reported as a regulator of bone mass in mice. Given that high systemic triiodothyronine (T3) levels in Mct8 knockout (KO) mice are still able to cause trabecular bone loss, alternative TH transporters must substitute for MCT8 function in bone. In this study, we analyzed the skeletal phenotypes of male Oatp1c1 KO and Mct10 KO mice, which are euthyroid, and male Mct8/Oatp1c1 and Mct8/Mct10 double KO mice, which have elevated circulating T3 levels, to unravel the role of TH transport in bone. MicroCT analysis showed no significant trabecular bone changes in Oatp1c1 KO mice at 4 weeks and 16 weeks of age compared with wild-type littermate controls, whereas 16-week-old Mct8/Oatp1c1 double KO animals displayed trabecular bone loss. At 12 weeks, Mct10 KO mice, but not Mct8/Mct10 double KO mice, had decreased trabecular femoral bone volume with reduced osteoblast numbers. By contrast, lack of Mct10 in 24-week-old mice led to trabecular bone gain at the femur with increased osteoblast numbers and decreased osteoclast numbers whereas Mct8/Mct10 double KO did not alter bone mass. Neither Mct10 nor Mct8/Mct10 deletion affected vertebral bone structures at both ages. In vitro, osteoblast differentiation and activity were impaired by Mct10 and Mct8/Mct10-deficiency. These data demonstrate that MCT10, but not OATP1C1, is a site- and age-dependent regulator of bone mass and turnover in male mice.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Osso e Ossos/metabolismo , Animais , Transporte Biológico , Fenômenos Biomecânicos , Osso Esponjoso/metabolismo , Diferenciação Celular , Fêmur/fisiologia , Homeostase , Masculino , Camundongos , Camundongos Knockout , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteócitos/citologia , Fenótipo , Simportadores/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Tri-Iodotironina/metabolismo , Microtomografia por Raio-X
11.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34718498

RESUMO

Adipose tissue, once thought to be an inert receptacle for energy storage, is now recognized as a complex tissue with multiple resident cell populations that actively collaborate in response to diverse local and systemic metabolic, thermal, and inflammatory signals. A key participant in adipose tissue homeostasis that has only recently captured broad scientific attention is the lymphatic vasculature. The lymphatic system's role in lipid trafficking and mediating inflammation makes it a natural partner in regulating adipose tissue, and evidence supporting a bidirectional relationship between lymphatics and adipose tissue has accumulated in recent years. Obesity is now understood to impair lymphatic function, whereas altered lymphatic function results in aberrant adipose tissue deposition, though the molecular mechanisms governing these phenomena have yet to be fully elucidated. We will review our current understanding of the relationship between adipose tissue and the lymphatic system here, focusing on known mechanisms of lymphatic-adipose crosstalk.


Assuntos
Tecido Adiposo/fisiologia , Sistema Linfático/fisiologia , Vasos Linfáticos/fisiologia , Adipócitos/citologia , Tecido Adiposo/metabolismo , Adiposidade , Animais , Diferenciação Celular , Células Endoteliais/metabolismo , Homeostase , Humanos , Inflamação , Lipídeos/química , Vasos Linfáticos/metabolismo , Camundongos , Obesidade/metabolismo
12.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34718519

RESUMO

Pancreatic ß-cells can secrete insulin via 2 pathways characterized as KATP channel -dependent and -independent. The KATP channel-independent pathway is characterized by a rise in several potential metabolic signaling molecules, including the NADPH/NADP+ ratio and α-ketoglutarate (αKG). Prolyl hydroxylases (PHDs), which belong to the αKG-dependent dioxygenase superfamily, are known to regulate the stability of hypoxia-inducible factor α. In the current study, we assess the role of PHDs in vivo using the pharmacological inhibitor dimethyloxalylglycine (DMOG) and generated ß-cell-specific knockout (KO) mice for all 3 isoforms of PHD (ß-PHD1 KO, ß-PHD2 KO, and ß-PHD3 KO mice). DMOG inhibited in vivo insulin secretion in response to glucose challenge and inhibited the first phase of insulin secretion but enhanced the second phase of insulin secretion in isolated islets. None of the ß-PHD KO mice showed any significant in vivo defects associated with glucose tolerance and insulin resistance except for ß-PHD2 KO mice which had significantly increased plasma insulin during a glucose challenge. Islets from both ß-PHD1 KO and ß-PHD3 KO had elevated ß-cell apoptosis and reduced ß-cell mass. Isolated islets from ß-PHD1 KO and ß-PHD3 KO had impaired glucose-stimulated insulin secretion and glucose-stimulated increases in the ATP/ADP and NADPH/NADP+ ratio. All 3 PHD isoforms are expressed in ß-cells, with PHD3 showing the most distinct expression pattern. The lack of each PHD protein did not significantly impair in vivo glucose homeostasis. However, ß-PHD1 KO and ß-PHD3 KO mice had defective ß-cell mass and islet insulin secretion, suggesting that these mice may be predisposed to developing diabetes.


Assuntos
Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Prolil Hidroxilases/metabolismo , Isoformas de Proteínas/química , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Apoptose , Regulação da Expressão Gênica , Glucose/metabolismo , Teste de Tolerância a Glucose , Homeostase , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ácidos Cetoglutáricos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADP/metabolismo , Fosforilação Oxidativa , Consumo de Oxigênio , Fenótipo , Domínios Proteicos
13.
J Agric Food Chem ; 70(1): 171-183, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34962394

RESUMO

Non-nutritive sweeteners are the most widely used food additives designed to provide sweetness and reduce caloric intake. Studies have confirmed a link between sweeteners and colitis, yet supporting scientific data remain exiguous and controversial. In this study, three common sweeteners (Saccharin sodium, Stevioside, and Sucralose) in acceptable daily intake dosage were added to water in order to determine their effects on dextran sodium sulfate-induced colitis in mice. Our results show that the three sweeteners meliorate colitis to varying degrees─Saccharin exerts the most pronounced effect, followed by Stevioside and Sucralose. Intake of sweeteners alleviates colitis symptoms, alters gut microbiota, reshapes the TH17/Treg balance, protects the intestinal barrier, and reduces inflammation. Most significantly, sweeteners can enhance the abundance of Mucispirillum and Alistipes, which are conducive to colitis recovery, and upregulate the expression of E-cadherin through the miR-15b/RECK/MMP-9 axis to improve intestinal barrier integrity. Moreover, by inhibiting the MMP-9/AKT/NF-κB pathway, inflammation is relieved, as reflected in the restoration of the Th17/Treg balance. Our results link the consumption of sweeteners to the remission of colitis, which provides new scientific evidence for the safe use of sweeteners.


Assuntos
Colite , MicroRNAs , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Colo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Homeostase , Metaloproteinase 9 da Matriz , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Sulfatos , Edulcorantes
14.
Methods Mol Biol ; 2343: 119-145, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34473318

RESUMO

The global pandemics of obesity and sedentarism are associated with poor quality of life and increased risks for development of inflammatory chronic diseases, including type 2 diabetes, cardiovascular diseases, and cancer. Physical activity is considered as an antidote to counteract the development of chronic sterile inflammatory diseases. Thus, we review the most promising exercise training protocols for promoting weight loss, improving glucose homeostasis, and reducing inflammation. We discuss the advantages and disadvantages of moderate-intensity continuous aerobic training, high-intensity aerobic training, and combined (aerobic + resistance) training. Our aim with this chapter is to provide evidence and guidance for choosing the most appropriate protocols of exercise training according to the goals of the patient.


Assuntos
Diabetes Mellitus Tipo 2 , Exercício Físico , Resistência à Insulina , Obesidade , Glicemia , Diabetes Mellitus Tipo 2/terapia , Glucose , Homeostase , Humanos , Inflamação , Obesidade/terapia , Qualidade de Vida
15.
Ann Anat ; 239: 151836, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34563672

RESUMO

Soy isoflavone genistein interplays with numerous physiological or pathophysiological processes during ageing. However, its protective role and underlying mechanisms of action in the regulation of calcium (Ca2+) and phosphate (Pi) homeostasis in an animal model of the andropause are yet to be fully clarified. Wistar male rats (16-month-old) were divided into sham-operated, orchidectomized, orchidectomized estradiol-treated (0.625 mg/kg b.m./day) and orchidectomized genistein-treated (30 mg/kg b.m./day) groups. Treatments were administered subcutaneously for 3 weeks, while the controls received vehicle alone. Estradiol treatment increased the expression level of fibroblast growth factor receptor (FGFR) and parathyroid hormone 1 receptor (PTH1R), and activated mitogen - activated protein kinase kinase 1/2 (MEK 1/2) signaling pathway in the kidneys. Genistein application induced a prominent gene and protein expression of Klotho and downregulated the expression of FGFR and PTH1R in the kidney of andropausal rats. Activation of protein kinase B (Akt) signalling pathway was observed, while MEK 1/2 signaling pathway wasn't altered after genistein treatment. The increase of 25 (OH) vitamin D in the serum and decrease in Ca2+ urine content was observed after genistein application. Our findings strongly suggest genistein as a potent biocompound with beneficial effects on the regulation of Ca2+ and Pi homeostasis, especially during aging process when the balance of mineral metabolism is impaired. These novel data provide closer insights into the physiological roles of genistein in the regulation of mineral homeostasis.


Assuntos
Andropausa , Cálcio , Genisteína , Sistema de Sinalização das MAP Quinases , Fosfatos , Animais , Modelos Animais de Doenças , Genisteína/farmacologia , Homeostase , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno , Orquiectomia , Ratos , Ratos Wistar
16.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166297, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34718119

RESUMO

Cell death is now understood to be a highly regulated process that contributes to normal development and tissue homeostasis, alongside its role in the etiology of various pathological conditions. Through detailed molecular analysis, we have come to know that all cells do not always die in the same way, and that there are at least 7 processes involved, including: apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, and autophagy-mediated cell death. These processes act as pieces in the mosaic of cardiomyocyte cell death, which come together depending on context and stimulus. This review details each individual process, as well as highlights how they come together to produce various cardiac pathologies. By knowing how the pieces go together we can aim towards the development of efficacious therapeutics, which will enable us to prevent cardiomyocyte loss in the face of stress, both reducing mortality and improving quality of life.


Assuntos
Autofagia/genética , Sistema Cardiovascular/metabolismo , Morte Celular/genética , Homeostase/genética , Sistema Cardiovascular/patologia , Ferroptose/genética , Humanos , Necrose Dirigida por Permeabilidade Transmembrânica da Mitocôndria/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Necroptose/genética , Necrose/genética , Parthanatos/genética , Piroptose/genética
17.
J Cell Biol ; 221(1)2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34747981

RESUMO

During sexual reproduction, the zygote must inherit exactly one centrosome (spindle pole body [SPB] in yeasts) from the gametes, which then duplicates and assembles a bipolar spindle that supports the subsequent cell division. Here, we show that in the fission yeast Schizosaccharomyces pombe, the fusion of SPBs from the gametes is blocked in polyploid zygotes. As a result, the polyploid zygotes cannot proliferate mitotically and frequently form supernumerary SPBs during subsequent meiosis, which leads to multipolar nuclear divisions and the generation of extra spores. The blockage of SPB fusion is caused by persistent SPB localization of Pcp1, which, in normal diploid zygotic meiosis, exhibits a dynamic association with the SPB. Artificially induced constitutive localization of Pcp1 on the SPB is sufficient to cause blockage of SPB fusion and formation of extra spores in diploids. Thus, Pcp1-dependent SPB quantity control is crucial for sexual reproduction and ploidy homeostasis in fission yeast.


Assuntos
Antígenos/metabolismo , Proteínas de Ciclo Celular/metabolismo , Homeostase , Meiose , Ploidias , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/citologia , Schizosaccharomyces/metabolismo , Corpos Polares do Fuso/metabolismo , Cromossomos Fúngicos/metabolismo , Esporos Fúngicos/metabolismo , Zigoto/citologia
18.
J Exp Med ; 219(1)2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34817548

RESUMO

Transcription factors (TFs) regulate cell fates, and their expression must be tightly regulated. Autoregulation is assumed to regulate many TFs' own expression to control cell fates. Here, we manipulate and quantify the (auto)regulation of PU.1, a TF controlling hematopoietic stem and progenitor cells (HSPCs), and correlate it to their future fates. We generate transgenic mice allowing both inducible activation of PU.1 and noninvasive quantification of endogenous PU.1 protein expression. The quantified HSPC PU.1 dynamics show that PU.1 up-regulation occurs as a consequence of hematopoietic differentiation independently of direct fast autoregulation. In contrast, inflammatory signaling induces fast PU.1 up-regulation, which does not require PU.1 expression or its binding to its own autoregulatory enhancer. However, the increased PU.1 levels induced by inflammatory signaling cannot be sustained via autoregulation after removal of the signaling stimulus. We conclude that PU.1 overexpression induces HSC differentiation before PU.1 up-regulation, only later generating cell types with intrinsically higher PU.1.


Assuntos
Diferenciação Celular/genética , Células-Tronco Hematopoéticas/metabolismo , Homeostase/genética , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Regulação para Cima/genética , Animais , Células Cultivadas , Expressão Gênica , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência/métodos , Proteínas Proto-Oncogênicas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Imagem com Lapso de Tempo/métodos , Transativadores/metabolismo
19.
Biochim Biophys Acta Mol Cell Res ; 1869(1): 119140, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599983

RESUMO

Translation of an mRNA represents a critical step during the expression of protein-coding genes. As mechanisms governing post-transcriptional regulation of gene expression are progressively unveiled, it is becoming apparent that transcriptional programs are not fully reflected in the proteome. Herein, we highlight a previously underappreciated post-transcriptional mode of regulation of gene expression termed translational buffering. In principle, translational buffering opposes the impact of alterations in mRNA levels on the proteome. We further describe three types of translational buffering: compensation, which maintains protein levels e.g. across species or individuals; equilibration, which retains pathway stoichiometry; and offsetting, which acts as a reversible mechanism that maintains the levels of selected subsets of proteins constant despite genetic alteration and/or stress-induced changes in corresponding mRNA levels. While mechanisms underlying compensation and equilibration have been reviewed elsewhere, the principal focus of this review is on the less-well understood mechanism of translational offsetting. Finally, we discuss potential roles of translational buffering in homeostasis and disease.


Assuntos
Homeostase , Biossíntese de Proteínas , Animais , Uso do Códon , Humanos , Processamento Pós-Transcricional do RNA , Proteínas Ribossômicas/metabolismo
20.
Biochim Biophys Acta Mol Cell Res ; 1869(1): 119138, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619164

RESUMO

The site-1 and site-2 proteases (S1P and S2P) were identified over 20 years ago, and the functions of both have been addressed in numerous studies ever since. Whereas S1P processes a set of substrates independently of S2P, the latter acts in concert with S1P in a mechanism, called regulated intramembrane proteolysis, that controls lipid metabolism and response to unfolded proteins. This review summarizes the molecular roles that S1P and S2P jointly play in these processes. As S1P and S2P deficiencies mainly affect connective tissues, yet with varying phenotypes, we discuss the segregated functions of S1P and S2P in terms of cell homeostasis and maintenance of the connective tissues. In addition, we provide experimental data that point at S2P, but not S1P, as a critical regulator of cell adaptation to proteotoxicity or lipid imbalance. Therefore, we hypothesize that S2P can also function independently of S1P activity.


Assuntos
Endopeptidases/metabolismo , Pró-Proteína Convertases/metabolismo , Proteólise , Serina Endopeptidases/metabolismo , Animais , Membrana Celular/metabolismo , Tecido Conjuntivo/enzimologia , Tecido Conjuntivo/metabolismo , Homeostase , Humanos
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