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Regulation of Stem Cell Fate by ROS-mediated Alteration of Metabolism
Ryu, Jung Min,Lee, Hyun Jik,Jung, Young Hyun,Lee, Ki Hoon,Kim, Dah Ihm,Kim, Jeong Yeon,Ko, So Hee,Choi, Gee Euhn,Chai, Ing Ing,Song, Eun Ju,Oh, Ji Young,Lee, Sei-Jung,Han, Ho Jae Korean Society for Stem Cell Research 2015 International journal of stem cells Vol.8 No.1
<P>Stem cells have attracted much attention due to their distinct features that support infinite self-renewal and differentiation into the cellular derivatives of three lineages. Recent studies have suggested that many stem cells both embryonic and adult stem cells reside in a specialized niche defined by hypoxic condition. In this respect, distinguishing functional differences arising from the oxygen concentration is important in understanding the nature of stem cells and in controlling stem cell fate for therapeutic purposes. ROS act as cellular signaling molecules involved in the propagation of signaling and the translation of environmental cues into cellular responses to maintain cellular homeostasis, which is mediated by the coordination of various cellular processes, and to adapt cellular activity to available bioenergetic sources. Thus, in this review, we describe the physiological role of ROS in stem cell fate and its effect on the metabolic regulation of stem cells.</P>
Lee, Ki Hoon,Lee, Sei-Jung,Lee, Hyun Jik,Choi, Gee Euhn,Jung, Young Hyun,Kim, Dah Ihm,Gabr, Amr Ahmed,Ryu, Jung Min,Han, Ho Jae Frontiers Media S.A. 2017 Frontiers in molecular neuroscience Vol.10 No.-
<P>Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by cognitive impairment and memory loss. Amyloid β1-42 (Aβ) and hyper-phosphorylation of microtubule-associated protein tau have been considered as major histological features in AD. However, the mechanism of how Aβ induces the hyper-phosphorylation of tau remains to be clarified. In the present study, we investigated the underlying cellular mechanisms of Aβ with regard to the cell cycle regulatory protein-mediated phosphorylation of tau in promoting neuronal cell death. The oligomer Aβ (5 μM) significantly increased the level of caspase 3 cleavage and has the ability to induce cytotoxicity in human neuroblastoma SK-N-MC cells. Aβ induced the degree of extracellular calcium influx via the L-type channel to facilitate the production of reactive oxygen species (ROS). Aβ signaling through ROS production is uniquely mediated by the activation of PI3K/Akt, which is in turn required for mammalian target of rapamycin complex 1 (mTORC1) phosphorylation. mTORC1 activated by Aβ further increased the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), a binding protein (4E-BP1) and p70S6K1 to stimulate the HIF1α synthesis responsible for the induction of cyclinD<SUB>1</SUB>/cyclin-dependent kinase 4 (CDK4) and cyclinE/CDK2, whereas it significantly attenuated the activation of autophagy. Aβ distinctively induced the CDK2-mediated phosphorylation of tau, which is responsible for microtubule destabilization in promoting neuronal apoptosis. In mouse hippocampal primary neurons, the apoptotic cell death induced by Aβ is highly susceptible to the mTORC1 signaling pathway. These results demonstrate that Aβ efficiently stimulates the mTORC1 signaling pathway to facilitate HIF1α synthesis and autophagy inhibition to promote the expression of cell cycle regulatory proteins, during which CDK2 uniquely stimulates tau phosphorylation for microtubule destabilization-mediated neuronal apoptosis.</P>