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题名: Tetrahydrobiopterin Protects against Radiation-induced Growth Inhibition in H9c2 Cardiomyocytes
作者: Zhang, ZY; Li, Y; Li, R; Zhang, AA; Shang, B; Yu, J; Xie, XD
收录类别: SCIE ; PubMed ; MEDLINE
出版日期: 2016-11-20
刊名: CHINESE MEDICAL JOURNAL
卷号: 129, 期号:22, 页码:2733-2740
期刊主办单位: 中华医学会
出版者: MEDKNOW PUBLICATIONS & MEDIA PVT LTD
出版地: MUMBAI
英文摘要: Background: Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOSs) for the synthesis of nitric oxide (NO). BH4 therapy can reverse the disease-related redox disequilibrium observed with BH4 deficiency. However, whether BH4 exerts a protective effect against radiation-induced damage to cardiomyocytes remains unknown. Methods: Clonogenic assays were performed to determine the effects of X-ray on H9c2 cells with or without BH4 treatment. The contents of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) in H9c2 cells were measured to investigate oxidative stress levels. The cell cycle undergoing radiation with or without BH4 treatment was detected using flow cytometry. The expression levels of proteins in the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/P53 signaling pathway, inducible NOS (iNOS), and endothelial NOS (eNOS) were examined using Western blotting. Results: X-ray radiation significantly inhibited the growth of H9c2 cells in a dose-dependent manner, whereas BH4 treatment significantly reduced the X-ray radiation-induced growth inhibition (control group vs. X-ray groups, respectively, P < 0.01). X-ray radiation induced LDH release, apoptosis, and GO/Gl peak accumulation, significantly increasing the level of MDA and the production of NO, and decreased the level of SOD (control group vs. X-ray groups, respectively, P < 0.05 or P < 0.01). By contrast, BH4 treatment can significantly reverse these processes (BH4 treatment groups vs. X-ray groups, P < 0.05 or P < 0.01). BH4 reversed the X-ray radiation-induced expression alterations of apoptosis-related molecules, including B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein, and caspase-3, and molecules of the PI3K/Akt/P53 signaling pathway. BH4 enhanced the production of NO in 2 Gy and 4 Gy radiated groups by upregulating eNOS protein expression and downregulating iNOS protein expression. Conclusions: BH4 treatment can protect against X-ray-induced cardiomyocyte injury, possibly by recoupling eNOS rather than iNOS. BH4 treatment also decreased oxidative stress in radiated H9c2 cells.
关键词: Endothelial Nitric Oxide Synthase ; Oxidative Stress ; Proliferation ; Radiation-induced Heart Disease ; Tetrahydrobiopterin
作者部门: [Zhang, Zheng-Yi ; Yu, Jing] Lanzhou Univ, Hosp 2, Dept Hypertens, 82 Cuiyingmen Rd, Lanzhou 730030, Gansu, Peoples R China ; [Zhang, Zheng-Yi ; Shang, Bo] Lanzhou Univ, Hosp 2, Dept Heart Failure, Lanzhou 730030, Gansu, Peoples R China ; [Li, Yi ; Zhang, An-An ; Xie, Xiao-Dong] Lanzhou Univ, Sch Basic Med Sci, Inst Med Genet, Lanzhou 730000, Gansu, Peoples R China ; [Li, Rui] Lanzhou Univ, Sch Stomatol, Lanzhou 730000, Gansu, Peoples R China
通讯作者: Yu, J (reprint author), Lanzhou Univ, Hosp 2, Dept Hypertens, 82 Cuiyingmen Rd, Lanzhou 730030, Gansu, Peoples R China.
学科分类: General & Internal Medicine
文章类型: Article
所属项目编号: National Natural Science Foundation of China [81270332] ; Gansu Province Health Industry Scientific Research Plan [GSWSKY-2014-33]
所属项目名称: 国家自然科学基金项目 ; 甘肃省卫生厅资助项目
项目资助者: NSFC ; GSPHD
语种: 英语
DOI: 10.4103/0366-6999.193455
ISSN号: 0366-6999
WOS记录号: WOS:000387990100014
PM记录号: 27824007
IR记录号: WOS:000387990100014
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内容类型: 期刊论文
URI标识: http://ir.lzu.edu.cn/handle/262010/188694
Appears in Collections:第二临床医学院_期刊论文

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Recommended Citation:
Zhang, ZY,Li, Y,Li, R,et al. Tetrahydrobiopterin Protects against Radiation-induced Growth Inhibition in H9c2 Cardiomyocytes[J]. CHINESE MEDICAL JOURNAL,2016,129(22):2733-2740.
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