title: BRD7 mediates hyperglycaemia-induced myocardial apoptosis via endoplasmic reticulum stress signalling pathway.
abstract: Bromodomain-containing protein 7 (BRD7) is a tumour suppressor that is known to regulate many pathological processes including cell growth, apoptosis and cell cycle. Endoplasmic reticulum (ER) stress-induced apoptosis plays a key role in diabetic cardiomyopathy (DCM). However, the molecular mechanism of hyperglycaemia-induced myocardial apoptosis is still unclear. We intended to determine the role of BRD7 in high glucose (HG)-induced apoptosis of cardiomyocytes. In vivo, we established a type 1 diabetic rat model by injecting a high-dose streptozotocin (STZ), and lentivirus-mediated short hairpin RNA (shRNA) was used to inhibit BRD7 expression. Rats with DCM exhibited severe myocardial remodelling, fibrosis, left ventricular dysfunction and myocardial apoptosis. The expression of BRD7 was up-regulated in the heart of diabetic rats, and inhibition of BRD7 had beneficial effects against diabetes-induced heart damage. In vitro, H9c2 cardiomyoblasts was used to investigate the mechanism of BRD7 in HG-induced apoptosis. Treating H9c2 cardiomyoblasts with HG elevated the level of BRD7 via activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and increased ER stress-induced apoptosis by detecting spliced/active X-box binding protein 1 (XBP-1s) and C/EBP homologous protein (CHOP). Furthermore, down-regulation of BRD7 attenuated HG-induced expression of CHOP via inhibiting nuclear translocation of XBP-1s without affecting the total expression of XBP-1s. In conclusion, inhibition of BRD7 appeared to protect against hyperglycaemia-induced cardiomyocyte apoptosis by inhibiting ER stress signalling pathway.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Qilu Hospital of Shandong University (Qingdao), Qingdao, Shandong, China.
authors.forename: Ying-Cui
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Xiang-Juan
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Ge
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D051742:Transcription Factor CHOP / Q000235:genetics*; D000071717:X-Box Binding Protein 1 / Q000235:genetics*; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D034741:RNA, Small Interfering; D051742:Transcription Factor CHOP; D000071717:X-Box Binding Protein 1; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C497251:Ddit3 protein, rat; C000605545:Xbp1 protein, rat
keywords: 
  CHOP
  ; BRD7; apoptosis; diabetic cardiomyopathy; endoplasmic reticulum stress