Autophagy activation: a novel mechanism of atorvastatin to protect mesenchymal stem cells from hypoxia and serum deprivation via AMP-activated protein kinase/mammalian target of rapamycin pathway.

Stem Cells and Development
Qian ZhangHui Xu

Abstract

Autophagy is a complex "self-eating" process and could be utilized for cell survival under stresses. Statins, which could reduce apoptosis in mesenchymal stem cells (MSCs) during both ischemia and hypoxia/serum deprivation (H/SD), have been proved to induce autophagy in some cell lines. We have previously shown that atorvastatin (ATV) could regulate AMP-activated protein kinase (AMPK), a positive modulator of autophagy, in MSCs. Thus, we hypothesized that autophagy activation through AMPK and its downstream molecule mammalian target of rapamycin (mTOR) may be a novel mechanism of ATV to protect MSCs from apoptosis during H/SD. Here, we demonstrated that H/SD induced autophagy in MSCs significantly as identified by increasing acidic vesicular organelle-positive cells, type II of light chain 3 (LC3-II) expression, and autophagosome formation. The levels of H/SD-induced apoptosis were increased by autophagy inhibitor 3-methyladenine (3-MA) while decreased by rapamycin, an autophagic inducer. ATV further enhanced the autophagic activity observed in MSCs exposed to H/SD. Treatment with 3-MA attenuated ATV-induced autophagy and abrogated the protective effects of ATV on MSC apoptosis, while rapamycin failed to cause additional effect...Continue Reading

References

Aug 25, 2004·The International Journal of Biochemistry & Cell Biology·Noboru Mizushima
Oct 26, 2005·Cell Death and Differentiation·P Codogno, A J Meijer
Apr 29, 2006·Cell Death and Differentiation·A Hamacher-BradyA B Gustafsson
Aug 3, 2006·The Journal of Biological Chemistry·Anne Hamacher-BradyRoberta A Gottlieb
Jan 17, 2007·Autophagy·Alfred J Meijer, Patrice Codogno
Jan 8, 2008·Biochemical and Biophysical Research Communications·Makoto Araki, Kiyoto Motojima
Feb 19, 2008·The Journal of Biological Chemistry·Huafeng ZhangGregg L Semenza
Feb 29, 2008·Nature·Noboru MizushimaDaniel J Klionsky
Jun 14, 2008·Cell Death and Differentiation·I PapandreouN C Denko
Sep 2, 2008·Neurobiology of Disease·Silvia CarloniWalter Balduini
Feb 5, 2009·Molecular Cancer Therapeutics·Vanessa MilanoJohn de Groot
Mar 28, 2009·Cell Death and Differentiation·A Eisenberg-LernerA Kimchi
May 2, 2009·Cell Death and Differentiation·Y ChenS B Gibson
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Henry C QuevedoJoshua M Hare
Sep 19, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Yue-Jin YangYong-Jian Geng
Dec 5, 2009·Cardiovascular Research·Narasimman GurusamyDipak K Das
Dec 26, 2009·Current Opinion in Cell Biology·Zhifen Yang, Daniel J Klionsky
Jun 16, 2010·Cell Research·Maryam MehrpourPatrice Codogno
Feb 15, 2011·Carcinogenesis·Cecilia G SanchezRadhika R Pochampally
Apr 20, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Hui XuQian Zhang

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Citations

Mar 16, 2013·EMBO Molecular Medicine·Huize PanJuan Carlos Izpisua Belmonte
Jun 7, 2012·Cellular and Molecular Life Sciences : CMLS·Kanchan PhadwalAnna Katharina Simon
Oct 24, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alex ZhavoronkovAlexey Moskalev
May 3, 2014·International Journal of Molecular Medicine·Parvaneh MehrbodAini Ideris
Apr 30, 2013·Micron : the International Research and Review Journal for Microscopy·Ida Perrotta
Aug 16, 2014·BioResearch Open Access·Sébastien SartYan Li
Aug 2, 2013·Antioxidants & Redox Signaling·Allen M AndresRoberta A Gottlieb
Dec 10, 2014·Archives of Toxicology·Fang YuntaoLu Rongzhu
Jun 3, 2015·International Journal of Molecular Medicine·Fengyun ZhangBo Yu
Nov 14, 2012·The International Journal of Biochemistry & Cell Biology·Jing ZhangXuefeng Liu
Oct 27, 2015·Cellular and Molecular Life Sciences : CMLS·Carlo RodolfoFrancesco Cecconi
Dec 30, 2014·British Journal of Pharmacology·Cécile Vindis
Jun 8, 2013·Biochimica Et Biophysica Acta·L B BuravkovaV Gogvadze
Aug 27, 2015·BioResearch Open Access·Ching-Ming YangShan-Hui Hsu
Feb 24, 2015·Molecular and Cellular Biochemistry·Wenzheng XiaMeng Hou
Mar 15, 2013·Autophagy·Jun-Lin GuanJue Zhang
Jan 13, 2015·Cellular and Molecular Life Sciences : CMLS·Shuo WangZusen Fan
Dec 18, 2014·Molecular Medicine Reports·Long WangZhuo-Jing Luo
Dec 31, 2014·Journal of Cardiovascular Translational Research·Yun LiDarren H Freed
Jan 31, 2015·Apoptosis : an International Journal on Programmed Cell Death·Xian-Yun WangXi Chen
Jul 29, 2016·Journal of Psychiatric Research·Fabiana Kalyne LudkaCarla Inês Tasca
Oct 28, 2016·Heart Failure Reviews·Peisen HuangYuejin Yang
Apr 7, 2017·Scientific Reports·Zhichao ZhangYan Li

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Methods Mentioned

BETA
electrophoresis
flow cytometric assay

Software Mentioned

Cell Quest
Quantity One

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