title: Neuregulin-1 suppresses cardiomyocyte apoptosis by activating PI3K/Akt and inhibiting mitochondrial permeability transition pore.
abstract: Neuregulin-1 (NRG-1) has been shown to attenuate cardiomyocyte apoptosis but the underlying signaling mechanism remains elusive. In this study, we focused on mitochondrial permeability transition pore (mPTP) opening and PI3K/Akt pathway to investigate the effects of NRG-1 on oxidative stress-induced apoptosis of cardiomyocyte. Human cardiac myocytes and neonatal rat cardiac myocytes were exposed to hydrogen peroxide with or without pre-treatment with recombinant human neuregulin-1 (rhNRG-1). Cell apoptosis and mPTP opening were assayed by flow cytometry and confocal microscopy. The activation of Akt was detected by western blot analysis. The results showed that H(2)O(2) induced cardiomyocyte apoptosis and activated mPTP. rhNRG-1 inhibited mPTP and activated Akt in the presence of H(2)O(2) and further protected the cells from H(2)O(2)-induced apoptosis. However, rhNRG-1 failed to inhibit mPTP opening and cell apoptosis in the presence of PI3K inhibitor LY294002. Taken together, these findings suggest that NRG-1 activates PI3K/Akt signaling and inhibits mPTP opening, and downstream apoptotic events in cardiac myocytes subjected to oxidative stress.
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Bingzhang
authors.initials: B
authors.lastname: Jie
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zhang
authors.forename: Xuesi
authors.initials: X
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Xin
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D020890:Neuregulin-1 / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D066247:Receptor, ErbB-4; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020169:Caspases; D066246:ErbB Receptors; D006861:Hydrogen Peroxide; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D020890:Neuregulin-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D066247:Receptor, ErbB-4; D011994:Recombinant Proteins; C587689:ERBB4 protein, human; C587691:Erbb4 protein, rat