PMID- 28685010 OWN - NLM STAT- MEDLINE DCOM- 20180131 LR - 20181113 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2017 DP - 2017 TI - Hydrogen Sulfide Inhibits Autophagic Neuronal Cell Death by Reducing Oxidative Stress in Spinal Cord Ischemia Reperfusion Injury. PG - 8640284 LID - 10.1155/2017/8640284 [doi] LID - 8640284 AB - Autophagy is upregulated in spinal cord ischemia reperfusion (SCIR) injury; however, its expression mechanism is largely unknown; moreover, whether autophagy plays a neuroprotective or neurodegenerative role in SCIR injury remains controversial. To explore these issues, we created an SCIR injury rat model via aortic arch occlusion. Compared with normal controls, autophagic cell death was upregulated in neurons after SCIR injury. We found that autophagy promoted neuronal cell death during SCIR, shown by a significant number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling- (TUNEL-) positive cells colabeled with the autophagy marker microtubule-associated protein 1 light chain 3, while the autophagy inhibitor 3-methyladenine reduced the number of TUNEL-positive cells and restored neurological and motor function. Additionally, we showed that oxidative stress was the main trigger of autophagic neuronal cell death after SCIR injury and N-acetylcysteine inhibited autophagic cell death and restored neurological and motor function in SCIR injury. Finally, we found that hydrogen sulfide (H(2)S) inhibited autophagic cell death significantly by reducing oxidative stress in SCIR injury via the AKT-the mammalian target of rapamycin (mTOR) pathway. These findings reveal that oxidative stress induces autophagic cell death and that H(2)S plays a neuroprotective role by reducing oxidative stress in SCIR. FAU - Xie, Lei AU - Xie L AUID- ORCID: 0000-0001-5435-7767 AD - Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. FAU - Yu, Sifei AU - Yu S AD - Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. FAU - Yang, Kai AU - Yang K AD - Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. FAU - Li, Changwei AU - Li C AUID- ORCID: 0000-0001-9324-4685 AD - Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. FAU - Liang, Yu AU - Liang Y AUID- ORCID: 0000-0002-1927-4875 AD - Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. AD - Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. LA - eng PT - Journal Article DEP - 20170608 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - YY9FVM7NSN (Hydrogen Sulfide) SB - IM MH - Animals MH - Autophagy/*physiology MH - Disease Models, Animal MH - Humans MH - Hydrogen Sulfide/*metabolism MH - Male MH - Oxidative Stress MH - Rats MH - Rats, Sprague-Dawley MH - Reperfusion Injury/*metabolism MH - Spinal Cord Ischemia/*metabolism PMC - PMC5480044 EDAT- 2017/07/08 06:00 MHDA- 2018/02/01 06:00 PMCR- 2017/06/08 CRDT- 2017/07/08 06:00 PHST- 2016/12/29 00:00 [received] PHST- 2017/04/01 00:00 [revised] PHST- 2017/04/23 00:00 [accepted] PHST- 2017/07/08 06:00 [entrez] PHST- 2017/07/08 06:00 [pubmed] PHST- 2018/02/01 06:00 [medline] PHST- 2017/06/08 00:00 [pmc-release] AID - 10.1155/2017/8640284 [doi] PST - ppublish SO - Oxid Med Cell Longev. 2017;2017:8640284. doi: 10.1155/2017/8640284. Epub 2017 Jun 8.