title: Endoplasmic reticulum oxidoreductin 1α mediates hepatic endoplasmic reticulum stress in homocysteine-induced atherosclerosis.
abstract: Endoplasmic reticulum (ER) stress is emerging as an important modulator of different pathological process and as a mechanism contributing to homocysteine (Hcy)-induced hepar injury. However, the molecular event that Hcy-induced ER stress in the hepar under the atherosclerosis background is currently unknown. Endoplasmic reticulum oxidoreductin 1α (ERO1α) plays a crucial role in maintaining ER stress function. In this study, we determined the expression of ERO1α in the hepar in hyperhomocysteinemia and the effect of ERO1α in hepacytes ER stress in the presence of Hcy. HHcy model was established by feeding the methionine diet in apolipoprotein-E-deficient (ApoE-/-) mice, and the hepatocytes were incubated with folate and different concentrations of Hcy. Our results showed that Hcy triggered ER stress characterized by an increased contents of glucose-regulated protein 78 (GRP78), protein kinase RNA-like ER kinase (PERK), activating transcription factor (ATF) 6 and X-box binding protein-1 (XBP-1). The ERO1α expressions in HHcy mice and Hcy-treated hepatocytes were decreased compared with those in ApoE-/- group and control hepacytes (P < 0.05), respectively. Knocking-down the expression of ERO1α with small-interfering RNA significantly augmented Hcy-induced ER stress. Meanwhile, the expressions of ER stress-related factor including GRP78, PERK, ATF6 and XBP-1, were significantly decreased when the ERO1α gene was over-expressed in hepacytes. Our results suggested that ERO1α may be involved in Hcy-induced hepar ER stress, and the inhibition of ERO1α expression can accelerate this process.
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yinju
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Clinical Examination, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Clinical Examination, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Clinical Examination, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Xuebo
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Shengchao
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan 750004, China yangwj04@126.com.
authors.forename: Yideng
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006710:Homocysteine / Q000009:adverse effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological
chemical_list: D001057:Apolipoproteins E; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D008562:Membrane Glycoproteins; D006710:Homocysteine; C405327:ERO1A protein, human; D010088:Oxidoreductases
keywords: atherosclerosis; endoplasmic reticulum oxidoreductin 1α; endoplasmic reticulum stress; homocysteine