Chronic ethanol consumption induces mitochondrial protein acetylation and oxidative stress in the kidney.
Chronic ethanol consumption induces mitochondrial protein acetylation and oxidative stress in the kidney.
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DOI：
10.1016/j.redox.2015.06.021
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发表时间：
2015-12
期刊：
影响因子：
11.4
通讯作者：
Fritz KS
中科院分区：
文献类型：
--
作者：
Harris PS;Roy SR;Coughlan C;Orlicky DJ;Liang Y;Shearn CT;Roede JR;Fritz KS
在这项研究中，我们提出了新的发现：长期摄入乙醇会诱导肾脏线粒体蛋白质过度乙酰化，并与肾脏氧化应激显著增加相关。酒精性肝病（ALD）的一个主要蛋白质组学特征是肝脏线粒体蛋白质乙酰化增加。蛋白质过度乙酰化已被证明会改变许多蛋白质的酶功能，并在调节代谢过程中起作用。肾脏线粒体过度乙酰化的靶点包括许多代谢和抗氧化途径，如脂质代谢、氧化磷酸化和氨基酸代谢，以及谷胱甘肽和硫氧还蛋白途径。蛋白质赖氨酸乙酰化的破坏有可能通过代谢失调和抗氧化能力下降损害肾功能。由于乙醇介导的肾脏氧化应激显著升高，我们强调了超氧化物歧化酶、过氧化物酶、谷胱甘肽还原酶和谷胱甘肽转移酶的乙酰化。由于氧化应激是乙醇诱导的肾毒性的一个已知因素，我们检测了蛋白质过度乙酰化和氧化应激的生化标志物。我们的结果表明，在我们为期6周的早期酒精性肾毒性模型中，蛋白质乙酰化增加，同时谷胱甘肽耗尽，半胱氨酸氧化还原电位改变，以及存在4 - 羟基壬烯醛（4 - HNE）对蛋白质的修饰。这些发现支持了这样一种假设：乙醇代谢导致线粒体代谢底物的流入，从而导致线粒体蛋白质过度乙酰化，并有可能影响线粒体代谢和抗氧化过程。
慢性乙醇代谢诱导肾脏线粒体蛋白质过度乙酰化。
乙醇诱导的过度乙酰化发生在代谢和抗氧化蛋白质上。
肾脏氧化应激的发生与线粒体蛋白质过度乙酰化相关。
In this study, we present the novel findings that chronic ethanol consumption induces mitochondrial protein hyperacetylation in the kidney and correlates with significantly increased renal oxidative stress. A major proteomic footprint of alcoholic liver disease (ALD) is an increase in hepatic mitochondrial protein acetylation. Protein hyperacetylation has been shown to alter enzymatic function of numerous proteins and plays a role in regulating metabolic processes. Renal mitochondrial targets of hyperacetylation include numerous metabolic and antioxidant pathways, such as lipid metabolism, oxidative phosphorylation, and amino acid metabolism, as well as glutathione and thioredoxin pathways. Disruption of protein lysine acetylation has the potential to impair renal function through metabolic dysregulation and decreased antioxidant capacity. Due to a significant elevation in ethanol-mediated renal oxidative stress, we highlight the acetylation of superoxide dismutase, peroxiredoxins, glutathione reductase, and glutathione transferase enzymes. Since oxidative stress is a known factor in ethanol-induced nephrotoxicity, we examined biochemical markers of protein hyperacetylation and oxidative stress. Our results demonstrate increased protein acetylation concurrent with depleted glutathione, altered Cys redox potential, and the presence of 4-HNE protein modifications in our 6-week model of early-stage alcoholic nephrotoxicity. These findings support the hypothesis that ethanol metabolism causes an influx of mitochondrial metabolic substrate, resulting in mitochondrial protein hyperacetylation with the potential to impact mitochondrial metabolic and antioxidant processes. Chronic ethanol metabolism induces mitochondrial protein hyperacetylation in the kidney. Ethanol-induced hyperacetylation occurs on metabolic and antioxidant proteins. The onset of renal oxidative stress correlates with mitochondrial protein hyperacetylation.