Autophagy Mediates Astrocyte Death During Zinc-Potentiated Ischemia--Reperfusion Injury

Biological Trace Element Research
Rong PanKe Jian Liu

Abstract

Pathological release of excess zinc ions and the resultant increase in intracellular zinc has been implicated in ischemic brain cell death, although the underlying mechanisms are not fully understood. Since zinc promotes the formation of the autophagic signal, reactive oxygen species (ROS), and increases autophagy, a known mechanism of cell death, we hypothesized that autophagy is involved in zinc-induced hypoxic cell death. To study this hypothesis, we determined the effect of zinc on autophagy and ROS generation in C8-D1A astrocytes subjected to hypoxia and rexoygenation (H/R), simulating ischemic stroke. C8-D1A astrocytes subjected to 3-h hypoxia and 18-h reoxygenation exhibited dramatically increased autophagy and astrocyte cell death in the presence of 100 μM zinc. Pharmacological inhibition of autophagy decreased zinc-potentiated H/R-induced cell death, while scavenging ROS reduced both autophagy and cell death caused by zinc-potentiated H/R. These data indicate that zinc-potentiated increases in ROS lead to over-exuberant autophagy and increased cell death in H/R-treated astrocytes. Furthermore, our elucidation of this novel mechanism indicates that modulation of autophagy, ROS, and zinc levels may be useful targets in d...Continue Reading

References

Jun 1, 1973·Teratology·J U Schweichel, H J Merker
Oct 29, 1993·Science·J T Coyle, P Puttfarcken
May 26, 1998·Journal of Neuropathology and Experimental Neurology·C K PetitoW A Pulsinelli
May 13, 1999·Brain Research. Molecular Brain Research·D LiuI A Simpson
Jan 5, 2000·Physiological Reviews·D G Nicholls, S L Budd
Oct 26, 2000·Trends in Pharmacological Sciences·J H WeissJ Y Koh
Jul 20, 2002·Free Radical Biology & Medicine·Charles D DetweilerRonald P Mason
Jan 15, 2005·Free Radical Biology & Medicine·Bernhard Schaller
May 14, 2005·Nature Reviews. Neuroscience·Christopher J FredericksonAshley I Bush
Aug 10, 2005·Proceedings of the National Academy of Sciences of the United States of America·Trent NguyenStephen M Massa
May 17, 2006·The Journal of Biological Chemistry·Yue XuJiahuai Han
Apr 20, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yi-Bing OuyangRona G Giffard
Jul 12, 2007·Molecular Medicine·Sherri L Galasso, Richard H Dyck
Sep 7, 2007·Trends in Cell Biology·Ruth Scherz-Shouval, Zvulun Elazar
Jan 24, 2008·Autophagy·Yasuo UchiyamaMasahiro Shibata
Mar 21, 2008·Journal of Molecular and Cellular Cardiology·Asa B Gustafsson, Roberta A Gottlieb
May 30, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tiina M KauppinenRaymond A Swanson
Mar 31, 2009·Antioxidants & Redox Signaling·Narasimman Gurusamy, Dipak K Das
Jun 5, 2010·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Jung Jin HwangJae-Young Koh
Jan 12, 2011·Neurobiology of Disease·Mi-Ha ParkJung Jin Hwang
May 31, 2011·Trends in Pharmacological Sciences·C William Shuttleworth, John H Weiss
Jun 7, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Kwang Woon KimBo Lu
Jun 7, 2012·Journal of the Neurological Sciences·Antonio FedericoElena Radi
Jul 13, 2012·Investigative Ophthalmology & Visual Science·Kyung Sook ChoJae-Young Koh
Sep 26, 2013·Biological Trace Element Research·J P Liuzzi, Chanwong Yoo

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Citations

Mar 18, 2016·Cellular and Molecular Neurobiology·Daniela KasprowskaBożena Gabryel
Jan 14, 2017·Expert Opinion on Therapeutic Targets·Jinghan FengJiangang Shen
Feb 3, 2018·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Juan P LiuzziChangwon Yoo
Jan 1, 2019·The International Journal of Neuroscience·Hongzhi ZhouXia Chen
Oct 26, 2018·Stroke; a Journal of Cerebral Circulation·Yongmei ZhaoKe Jian Liu
May 21, 2017·The Journal of Biological Chemistry·Binbin Ding, Qing Zhong
Jun 12, 2021·Frontiers in Immunology·Tamiris Lameira BittencourtRoberta Olmo Pinheiro
Jul 9, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Wenzhe WangWenyuan Gao

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