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regulation of mitochondrial function and endoplasmic reticulum stress by nitric oxide in pluripotent stem cells

World Journal of Stem Cells 2017年第2期9卷 26-36页

作者： Estefania Caballano-Infantes José Terron-Bautista Amparo Beltrán-Povea Gladys M Cahuana Bernat Soria Hajji Nabil Francisco J Bedoya juan r tejedo Andalusian Center for Molecular Biology and regenerative Medicine-University Pablo de Olavide 41092 SevilleSpain Biomedical research Network on Diabetes and related Metabolic Diseases(CIBErDEM) Instituto de Salud CarlosⅢ28029 MadridSpain Andalusian Center for Molecular Biology and regenerative Medicine(CABIMEr) 41092 SevilleSpain Andalusian Center for Molecular Biology and regenerative Medicine Fundación Progreso y Salud41092 SevilleSpain Centre for Pharmacology and Therapeutics Division of Experimental MedicineImperial College LondonHammersmith Hospital CampusLondon W12 0NNUnited Kingdom

Mitochondrial dysfunction and endoplasmic reticulum stress(ErS) are global processes that are interrelated and regulated by several stress factors. Nitric oxide(NO) is a multifunctional biomolecule with many varieties of physiological and pathological functions, such as the regulation of cytochrome c inhibition and activation of the immune response, ErS and DNA damage; these actions are dose-dependent. It has been reported that in embryonic stem cells, NO has a dual role, controlling differentiation, survival and pluripotency, but the molecular mechanisms by which it modulates these functions are not yet known. Low levels of NO maintain pluripotency and induce mitochondrial biogenesis. It is well established that NO disrupts the mitochondrial respiratory chain and causes changes in mitochondrial Ca^(2+) flux that induce ErS. Thus, at high concentrations, NO becomes a potential differentiation agent due to the relationship between ErS and the unfolded protein response in many differentiated cell lines. Nevertheless, many studies have demonstratedthe need for physiological levels of NO for a proper ErS response. In this review, we stress the importance of the relationships between NO levels, ErS and mitochondrial dysfunction that control stem cell fate as a new approach to possible cell therapy strategies.

关键词： Endoplasmic reticulum stress Mitochondrial function Nitric oxide Pluripotency Cell differentiation Mitochondrial biogenesis

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role of nitric oxide in the maintenance of pluripotency and regulation of the hypoxia response in stem cells

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World Journal of Stem Cells 2015年第3期7卷 605-617页

作者： Amparo Beltran-Povea Estefania Caballano-Infantes Carmen Salguero-Aranda Franz Martín Bernat Soria Francisco J Bedoya juan r tejedo Gladys M Cahuana Andalusian Center for Molecular Biology and regenerative Medicine-University Pablo de Olavide CIBERDEM RED-TERCEL 41092 Seville Spain Andalusian Center for Molecular Biology and regenerative Medicine (CABIMEr) -Fundación Progreso y Salud CIBERDEM RED-TERCEL 41092 Seville Spain

Stem cell pluripotency and differentiation are global processes regulated by several pathways that have been studied intensively over recent years. Nitric oxide(NO) is an important molecule that affects gene expression at the level of transcription and translation and regulates cell survival and proliferation in diverse cell types. In embryonic stem cells NO has a dual role, controlling differentiation and survival, but the molecular mechanisms by which it modulates these functions are not completely defined. NO is a physiological regulator of cell respiration through the inhibition of cytochrome c oxidase. Many researchers have been examining the role that NO plays in other aspects of metabolism such as the cellular bioenergetics state, the hypoxia response and the relationship of these areas to stem cell stemness.

关键词： Pluripotency Differentiation Nitric oxide Metabolism Hypoxia Stem cell

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