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UVB 诱导的氧化应激对正常人类上皮角质形成细胞中蛋白质表达和特定蛋白质氧化的影响:一种蛋白质组学方法。

Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach.

机构信息

Department of Biochemical Sciences, "Sapienza" University of Rome - P.le A. Moro, 5 - 00185 Rome, Italy.

CNR Institute of Molecular Biology and Pathology - P.le A. Moro, 5 - 00185 Rome, Italy.

出版信息

Proteome Sci. 2010 Mar 18;8:13. doi: 10.1186/1477-5956-8-13.

Abstract

BACKGROUND

The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes.

RESULTS

The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized.

CONCLUSIONS

Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.

摘要

背景

太阳紫外线照射的 UVB 成分是人类皮肤癌发展的主要危险因素之一。UVB 暴露会引发活性氧(ROS)的大量产生,这些 ROS 负责对蛋白质、DNA、RNA 和脂质造成氧化损伤。为了研究 UVB 照射对皮肤细胞的生物学影响,我们采用平行蛋白质组学方法来分析蛋白质表达谱,并鉴定正常人类上皮角质形成细胞中氧化修饰的蛋白质。

结果

在 UVB 暴露的细胞中,有十五种蛋白质的表达水平发生了差异调节——这些蛋白质参与维持细胞骨架的完整性、清除受损蛋白质和热休克反应——这表明为了对抗/中和由 UVB 引起的 ROS 的毒性作用,会产生适当的反应。另一方面,氧化还原蛋白质组学方法揭示了七种蛋白质——参与细胞黏附、细胞-细胞相互作用和蛋白质折叠——被选择性氧化。

结论

尽管存在广泛而协调良好的细胞反应,但在 UVB 照射的人类上皮角质形成细胞中,也会同时发生特定蛋白质的显著氧化。这些修饰(即可能功能失调)的蛋白质可能导致细胞内稳态受损,从而最终促进细胞退化、衰老或癌变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05a0/3161386/cecb7bc731a6/1477-5956-8-13-1.jpg

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