title: A novel mechanism by which SDF-1β protects cardiac cells from palmitate-induced endoplasmic reticulum stress and apoptosis via CXCR7 and AMPK/p38 MAPK-mediated interleukin-6 generation.
abstract: We studied the protective effect of stromal cell-derived factor-1β (SDF-1β) on cardiac cells from lipotoxicity in vitro and diabetes in vivo. Exposure of cardiac cells to palmitate increased apoptosis by activating NADPH oxidase (NOX)-associated nitrosative stress and endoplasmic reticulum (ER) stress, which was abolished by pretreatment with SDF-1β via upregulation of AMP-activated protein kinase (AMPK)-mediated p38 mitogen-activated protein kinase (MAPK) phosphorylation and interleukin-6 (IL-6) production. The SDF-1β cardiac protection could be abolished by inhibition of AMPK, p38 MAPK, or IL-6. Activation of AMPK or addition of recombinant IL-6 recaptured a similar cardiac protection. SDF-1β receptor C-X-C chemokine receptor type 4 (CXCR4) antagonist AMD3100 or CXCR4 small interfering RNA could not, but CXCR7 small interfering RNA completely abolished SDF-1β's protection from palmitate-induced apoptosis and activation of AMPK and p38 MAPK. Administration of SDF-1β to diabetic rats, induced by feeding a high-fat diet, followed by a small dose of streptozotocin, could significantly reduce cardiac apoptosis and increase AMPK phosphorylation along with prevention of diabetes-induced cardiac oxidative damage, inflammation, hypertrophy, and remodeling. These results showed that SDF-1β protects against palmitate-induced cardiac apoptosis, which is mediated by NOX-activated nitrosative damage and ER stress, via CXCR7, to activate AMPK/p38 MAPK-mediated IL-6 generation. The cardiac protection by SDF-1β from diabetes-induced oxidative damage, cell death, and remodeling was also associated with AMPK activation.
authors: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors: Yuguang
authors: Y
authors: Zhao
authors: Yi
authors: Y
authors: Tan
authors: Shugang
authors: S
authors: Xi
authors: Yunqian
authors: Y
authors: Li
authors: Cai
authors: C
authors: Li
authors: Jiuwei
authors: J
authors: Cui
authors: Xiaoqing
authors: X
authors: Yan
authors: Xiaokun
authors: X
authors: Li
authors: Guanjun
authors: G
authors: Wang
authors: Wei
authors: W
authors: Li
authors: Lu
authors: L
authors: Cai
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001596:Benzylamines; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000378:metabolism* / Q000494:pharmacology; D000080027:Cyclams; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D059305:Diet, High-Fat; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C501898:Ackr3 protein, rat; D001596:Benzylamines; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D015850:Interleukin-6; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D019308:Palmitic Acid; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase; C088327:plerixafor