Autophagy is involved in the ischemic preconditioning.
Autophagy is a key pathway for the clearance of damaged organelles. Ischemic preconditioning (IPC) and autophagy are enhanced by mild hypoxic insults, but the association between autophagy and IPC remains unclear. We investigated the existence and role of autophagy in IPC. In an in vitro PC12 cell model, IPC increased generation and degradation of autophagosomes, as revealed by increased LC3-II bands, cathepsin D positive cells, lysosomal activity and autophagic vacuoles on electron microscopy. Autophagic activity was blocked using 3-methyladenine during IPC, and cell viabilities were measured using FASC and WST-1 assays. Inhibition of autophagy, especially during reperfusion or lethal oxygen-glucose deprivation periods ameliorated the neuroprotective effects of IPC. Moreover, inhibiting autophagy also attenuated Hsp70 upregulation induced by IPC. These findings imply that autophagy participates in IPC-induced neuroprotection, and that autophagy might provide a means of neuroprotection against cerebral ischemia.
Park
Hee-Kwon
HK
Stroke & Stem Cell Laboratory, Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Chu
Kon
K
Jung
Keun-Hwa
KH
Lee
Soon-Tae
ST
Bahn
Jae-Joon
JJ
Kim
Manho
M
Lee
Sang Kun
SK
Roh
Jae-Kyu
JK
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002402:Cathepsin D / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D016716:PC12 Cells; D010588:Phagosomes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D013778:Tetrazolium Salts
C110656:2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; D018840:HSP70 Heat-Shock Proteins; D013778:Tetrazolium Salts; C025946:3-methyladenine; D002402:Cathepsin D; D000225:Adenine