二甲基精氨酸二甲基氨基水解酶-1在tBHP诱导的氧化应激下表达增加,调节PCa细胞中一氧化氮的产生,减弱线粒体ROS介导的细胞凋亡。

IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sakkarai Mohamed Asha Parveen , Karthik Reddy Kami Reddy , Ramesh Ummanni
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引用次数: 1

摘要

二甲基精氨酸二甲基氨基水解酶-1(DDAH1)的表达在包括癌症(PCa)在内的不同癌症中频繁升高,并通过代谢内源性一氧化氮合酶(NOS)抑制剂增强肿瘤细胞中一氧化氮(NO)的产生。DDAH1保护前列腺癌细胞免于细胞死亡并促进存活。在本研究中,我们研究了DDAH1的细胞保护作用,并确定了DDAH1在肿瘤微环境中保护细胞的机制。对具有DDAH1稳定过表达的PCa细胞的蛋白质组学分析已经确定氧化应激相关活性改变。氧化应激促进癌症细胞增殖、存活并引起化疗耐药性。一种已知的氧化应激诱导剂,过氧化叔丁基(tBHP)对前列腺癌细胞的处理导致DDAH1水平升高,该水平积极参与保护前列腺癌细胞免受氧化应激诱导的细胞损伤。在PC3-DDAH1-细胞中,tBHP处理导致mROS水平升高,表明DDAH1-的缺失增加了氧化应激,并最终导致细胞死亡。在氧化应激下,SIRT1控制的核Nrf2正向调节PC3细胞中DDAH1的表达。在PC3-DDAH1+细胞中,与野生型细胞相比,tBHP诱导的DNA损伤具有良好的耐受性,而PC3-DDAH1-对tBHP变得敏感。在PC3细胞中,tBHP暴露增加了NO和GSH的产生,这可能是克服氧化应激的抗氧化防御。此外,在tBHP处理的PCa细胞中,DDAH1控制Bcl2、活性PARP和胱天蛋白酶3的表达。总之,这些结果证实了DDAH1参与抗氧化防御系统并促进细胞存活。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dimethylarginine Dimethylaminohydrolase - 1 expression is increased under tBHP-induced oxidative stress regulates nitric oxide production in PCa cells attenuates mitochondrial ROS-mediated apoptosis

Dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression is frequently elevated in different cancers including prostate cancer (PCa) and enhances nitric oxide (NO) production in tumor cells by metabolising endogenous nitric oxide synthase (NOS) inhibitors. DDAH1 protects the PCa cells from cell death and promotes survival. In this study, we have investigated the cytoprotective role of DDAH1 and determined the mechanism of DDAH1 in protecting the cells in tumor microenvironment. Proteomic analysis of PCa cells with stable overexpression of DDAH1 has identified that oxidative stress-related activity is altered. Oxidative stress promotes cancer cell proliferation, survival and causes chemoresistance. A known inducer of oxidative stress, tert-Butyl Hydroperoxide (tBHP) treatment to PCa cells led to elevated DDAH1 level that is actively involved in protecting the PCa cells from oxidative stress induced cell damage. In PC3-DDAH1 cells, tBHP treatment led to higher mROS levels indicating that the loss of DDAH1 increases the oxidative stress and eventually leads to cell death. Under oxidative stress, nuclear Nrf2 controlled by SIRT1 positively regulates DDAH1 expression in PC3 cells. In PC3-DDAH1+ cells, tBHP induced DNA damage is well tolerated compared to wild-type cells while PC3-DDAH1 became sensitive to tBHP. In PC3 cells, tBHPexposure has increased the production of NO and GSH which may be acting as an antioxidant defence to overcome oxidative stress. Furthermore, in tBHP treated PCa cells, DDAH1 is controlling the expression of Bcl2, active PARP and caspase 3. Taken together, these results confirm that DDAH1 is involved in the antioxidant defence system and promotes cell survival.

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来源期刊
Nitric oxide : biology and chemistry
Nitric oxide : biology and chemistry 生物-生化与分子生物学
CiteScore
7.50
自引率
7.70%
发文量
74
审稿时长
52 days
期刊介绍: Nitric Oxide includes original research, methodology papers and reviews relating to nitric oxide and other gasotransmitters such as hydrogen sulfide and carbon monoxide. Special emphasis is placed on the biological chemistry, physiology, pharmacology, enzymology and pathological significance of these molecules in human health and disease. The journal also accepts manuscripts relating to plant and microbial studies involving these molecules.
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