PMID- 27246638 OWN - NLM STAT- MEDLINE DCOM- 20180131 LR - 20220408 IS - 1089-8611 (Electronic) IS - 1089-8603 (Linking) VI - 58 DP - 2016 Aug 31 TI - Enhanced nitric oxide-mediated autophagy contributes to the hepatoprotective effects of ischemic preconditioning during ischemia and reperfusion. PG - 10-9 LID - S1089-8603(16)30059-3 [pii] LID - 10.1016/j.niox.2016.05.007 [doi] AB - Ischemic preconditioning (IPC) protects against liver ischemia/reperfusion (I/R) injury. Autophagy is an essential cytoprotective system that is rapidly activated by multiple stressors. Nitric oxide (NO) acts as an inducer of IPC. We examined the impact of autophagy in liver IPC and its regulation by NO. Male C57BL/6 mice were subjected to 60 min of hepatic ischemia followed by 6 h of reperfusion. IPC was achieved for 10 min of ischemia followed by 10 min of reperfusion prior to sustained ischemia. N(omega)-Nitro-l-arginine methyl ester (L-NAME, 15 mg/kg, i.v., all NOS inhibitor) and aminoguanidine (AG, 10 mg/kg, i.v., iNOS inhibitor) were injected 10 min before IPC. SB203580 (10 mg/kg, i.p., p38 inhibitor) was injected 30 min before IPC. I/R increased serum alanine aminotransferase activity. IPC attenuated this increase, which was abolished by L-NAME, but not AG. Microtubule-associated protein-1 light chain 3-II levels increased and p62 protein levels decreased after I/R; these changes were augmented by IPC and abolished by L-NAME. I/R increased liver protein expression of autophagy-related protein (Atg)12-Atg5 complex and lysosome-associated membrane protein-2. IPC augmented the expression of these proteins, which were abolished by L-NAME, but not AG. IPC also augmented the level of phosphorylated p38 MAPK induced by I/R and this phosphorylation was abolished by L-NAME. Our findings suggest that IPC-mediated NO protects against I/R-induced liver injury by enhancing autophagic flux. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Shin, Jun-Kyu AU - Shin JK AD - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. FAU - Kang, Jung-Woo AU - Kang JW AD - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. FAU - Lee, Sun-Mee AU - Lee SM AD - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: sunmee@skku.edu. LA - eng PT - Journal Article DEP - 20160528 PL - United States TA - Nitric Oxide JT - Nitric oxide : biology and chemistry JID - 9709307 RN - 0 (Guanidines) RN - 0 (Imidazoles) RN - 0 (Map1lc3b protein, mouse) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Pyridines) RN - 31C4KY9ESH (Nitric Oxide) RN - 886U3H6UFF (Chloroquine) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - OU13V1EYWQ (SB 203580) RN - SCQ4EZQ113 (pimagedine) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - *Autophagy MH - Chloroquine/pharmacology MH - Guanidines/pharmacology MH - Imidazoles/pharmacology MH - Ischemia/pathology/*prevention & control MH - *Ischemic Preconditioning MH - Liver/*blood supply/pathology MH - Liver Diseases/pathology/*prevention & control MH - Male MH - Mice, Inbred C57BL MH - Microtubule-Associated Proteins/metabolism MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Nitric Oxide/*metabolism MH - Pyridines/pharmacology MH - Reperfusion Injury/*prevention & control MH - p38 Mitogen-Activated Protein Kinases/metabolism OTO - NOTNLM OT - Autophagy OT - Ischemic preconditioning OT - Liver OT - Nitric oxide OT - p38 MAPK EDAT- 2016/06/02 06:00 MHDA- 2018/02/01 06:00 CRDT- 2016/06/02 06:00 PHST- 2016/04/06 00:00 [received] PHST- 2016/05/25 00:00 [revised] PHST- 2016/05/27 00:00 [accepted] PHST- 2016/06/02 06:00 [entrez] PHST- 2016/06/02 06:00 [pubmed] PHST- 2018/02/01 06:00 [medline] AID - S1089-8603(16)30059-3 [pii] AID - 10.1016/j.niox.2016.05.007 [doi] PST - ppublish SO - Nitric Oxide. 2016 Aug 31;58:10-9. doi: 10.1016/j.niox.2016.05.007. Epub 2016 May 28.