title: Chronic stress and excessive glucocorticoid exposure both lead to altered Neuregulin-1/ErbB signaling in rat myocardium.
abstract: Exposure to chronic stress or excess glucocorticoids is associated with the development of depression and heart disease, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in cardiac function, much is still unknown concerning the biological link between NRG1/ErbB pathway and the stress-induced comorbidity of depression and cardiac dysfunction. Therefore, we examined the protein expression of NRG1 and ErbB receptors in the myocardium of rats following chronic unpredictable mild stress (CUMS) or rats treated with two different doses (0.2 and 2mg/kg/day, respectively) of dexamethasone (Dex). The stressed rats showed elevated expression of NRG1 and phosphorylated ErbB4 (pErbB4) in the myocardium, whereas ErbB2 and pErbB2 were inhibited. The lower dose of Dex enhanced myocardial NRG1/ErbB signaling, but as the dose is increased, while ErbB4 remained activated, the expression of ErbB2 and pErbB2 became compromised. Both CUMS and 2mg/kg of Dex suppressed the downstream Akt and ERK phosphorylation. Although the lower dose of Dex increased myocardial antiapoptotic Bcl-xl expression, a significant decrease of Bcl-xl expression was found in rats treated with the higher dose. Meanwhile, both CUMS and two different doses of Dex induced proapoptotic Bax level. Combined, our data firstly showed (mal)adaptive responses of NRG1/ErbB system in the stressed heart, indicating the potential involvement of NRG1/ErbB pathway in the stress-induced cardiac dysfunction.
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Dang
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha 410010, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China.
authors.forename: Ranyao
authors.initials: R
authors.lastname: Yang
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China. Electronic address: jpoet89@126.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020890:Neuregulin-1 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D020890:Neuregulin-1; D003907:Dexamethasone; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Chronic unpredictable mild stress; Depression; Dexamethasone; Heart disease; Neuregulin-1