PMID- 27795806 OWN - NLM STAT- MEDLINE DCOM- 20170714 LR - 20181113 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2016 DP - 2016 TI - C1q/TNF-Related Protein 9 Protects Diabetic Rat Heart against Ischemia Reperfusion Injury: Role of Endoplasmic Reticulum Stress. PG - 1902025 LID - 1902025 AB - As a newly identified adiponectin paralog, C1q/TNF-related protein 9 (CTRP9) reduces myocardial ischemia reperfusion (IR) injury through partially understood mechanisms. In the present study, we sought to identify the role of endoplasmic reticulum stress (ERS) in CTRP9 induced cardioprotection in diabetic heart. Isolated hearts from high-fat-diet (HFD) induced type 2 diabetic Sprague-Dawley rats were subjected to ex vivo IR protocol via a Langendorff apparatus at the presence of globular CTRP9. CTRP9 significantly improved post-IR heart function and reduced cardiac infarction, cardiomyocytes apoptosis, Caspase-3, Caspase-9, Caspase-12, TNF-alpha expression, and lactate dehydrogenase activity. The cardioprotective effect of CTRP9 was associated with reduced ERS and increased expression of disulfide-bond A oxidoreductase-like protein (DsbA-L) in diabetic heart. CTRP9 reduced ERS in thapsigargin (TG) treated cardiomyocytes and protected endoplasmic reticulum (ER) stressed H9c2 cells against simulated ischemia reperfusion (SIR) injury, concurrent with increased expression of DsbA-L. Knockdown of DsbA-L increased ERS and attenuated CTRP9 induced protection against SIR injury in H9c2 cells. Our findings demonstrated for the first time that CTRP9 exerts cardioprotection by reducing ERS in diabetic heart through increasing DsbA-L. FAU - Bai, Sanxing AU - Bai S AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Cheng, Liang AU - Cheng L AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Yang, Yang AU - Yang Y AD - Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China. FAU - Fan, Chongxi AU - Fan C AD - Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an 710038, China. FAU - Zhao, Dajun AU - Zhao D AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Qin, Zhigang AU - Qin Z AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Feng, Xiao AU - Feng X AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Zhao, Lin AU - Zhao L AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Ma, Jipeng AU - Ma J AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Wang, Xiaowu AU - Wang X AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Yang, Jian AU - Yang J AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Xu, Xuezeng AU - Xu X AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Yi, Dinghua AU - Yi D AUID- ORCID: 0000-0001-8194-8837 AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. FAU - Yi, Wei AU - Yi W AUID- ORCID: 0000-0001-6478-6346 AD - Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. LA - eng GR - K99 AA020514/AA/NIAAA NIH HHS/United States GR - R00 AA020514/AA/NIAAA NIH HHS/United States GR - R01 AA020919/AA/NIAAA NIH HHS/United States PT - Journal Article DEP - 20161004 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Adiponectin) RN - EC 2.5.1.18 (Glutathione Transferase) SB - IM MH - Adiponectin/*pharmacology MH - Animals MH - Cell Line MH - Diabetes Mellitus, Experimental/metabolism MH - Endoplasmic Reticulum Stress/*drug effects/physiology/radiation effects MH - Gene Knockdown Techniques MH - Glutathione Transferase/genetics/metabolism MH - Heart/drug effects/radiation effects MH - Isolated Heart Preparation MH - Male MH - Myocardial Reperfusion Injury/metabolism/*prevention & control MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction PMC - PMC5067328 EDAT- 2016/11/01 06:00 MHDA- 2017/07/15 06:00 PMCR- 2016/10/04 CRDT- 2016/11/01 06:00 PHST- 2016/03/15 00:00 [received] PHST- 2016/08/06 00:00 [revised] PHST- 2016/08/28 00:00 [accepted] PHST- 2016/11/01 06:00 [pubmed] PHST- 2017/07/15 06:00 [medline] PHST- 2016/11/01 06:00 [entrez] PHST- 2016/10/04 00:00 [pmc-release] AID - 10.1155/2016/1902025 [doi] PST - ppublish SO - Oxid Med Cell Longev. 2016;2016:1902025. doi: 10.1155/2016/1902025. Epub 2016 Oct 4.