RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway.
Radiation-induced heart disease (RIHD), which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF)-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway.
Department of Radiotherapy, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Anxin
A
Gu
Department of Radiotherapy, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Yamin
Y
Jie
Department of Human Anatomy, Harbin Medical University, Harbin, Heilongjiang, China.
Liang
L
Sun
Department of Radiotherapy, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Shuping
S
Zhao
Department of Radiotherapy, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Mingyan
M
E
Department of Radiotherapy, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Qingshan
Q
You
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects* / Q000528:radiation effects*; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D020890:Neuregulin-1 / Q000627:therapeutic use*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D056564:Sirtuin 1 / Q000378:metabolism
D002316:Cardiotonic Agents; D020890:Neuregulin-1; D011837:Radiation-Protective Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D056564:Sirtuin 1; C117467:neuregulin beta; C483804:Erbb2 protein, rat; C488368:Sirt1 protein, rat