title: Baicalin protects the cardiomyocytes from ER stress-induced apoptosis: inhibition of CHOP through induction of endothelial nitric oxide synthase.
abstract: Baicalin, the main active ingredient of the Scutellaria root, exerts anti-oxidant and anti-apoptotic effects in cardiovascular diseases. However, the therapeutic mechanism of baicalin remains unknown. Cultured neonatal rat cardiomyocytes were pre-treated with baicalin (0-50 µM) for 24 h, and subsequently treated with tunicamycin (100 ng/ml). Cell viability was detected by MTT assay, and cell damage was determined by LDH release and TUNEL assay. The expression of CHOP, JNK, caspase-3, eNOS was analyzed by western blot. NO was measured by DAF-FM staining. As a result, treatment with baicalin significantly reduced apoptosis induced by ER stress inducer tunicamycin in cardiomyocytes. Molecularly, baicalin ameliorated tunicamycin-induced ER stress by downregulation of CHOP. In addition, baicalin inverted tunicamycin-induced decreases of eNOS mRNA and protein levels, phospho eNOS and NO production through CHOP pathway. However, the protective effects of baicalin were significantly decreased in cardiomyocytes treated with L-NAME, which suppressed activation of nitric oxide synthase. In conclusion, our results implicate that baicalin could protect cardiomyocytes from ER stress-induced apoptosis via CHOP/eNOS/NO pathway, and suggest the therapeutic values of baicalin against ER stress-associated cardiomyocyte apoptosis.
authors: Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China ; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China ; Department of Cardiology, Hainan Branch of PLA General Hospital, Sanya, China.
authors: Mingzhi
authors: M
authors: Shen
authors: Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Lin
authors: L
authors: Wang
authors: Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
authors: Guodong
authors: G
authors: Yang
authors: Department of Urology, Wuhan General Hospital, Guangzhou Command, PLA, Wuhan, China.
authors: Lei
authors: L
authors: Gao
authors: Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Bo
authors: B
authors: Wang
authors: Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Xiaowang
authors: X
authors: Guo
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Chao
authors: C
authors: Zeng
authors: Department of Cardiology, Hainan Branch of PLA General Hospital, Sanya, China.
authors: Yong
authors: Y
authors: Xu
authors: Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
authors: Liangliang
authors: L
authors: Shen
authors: Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Ke
authors: K
authors: Cheng
authors: Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Yuesheng
authors: Y
authors: Xia
authors: Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Xiumin
authors: X
authors: Li
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Haichang
authors: H
authors: Wang
authors: Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
authors: Li
authors: L
authors: Fan
authors: Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Xiaoming
authors: X
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D005419:Flavonoids; D014415:Tunicamycin; D051742:Transcription Factor CHOP; C038044:baicalin; D052250:Nitric Oxide Synthase Type III