The Protein Deacetylase SIRT3 Prevents Oxidative Stress-induced Keratinocyte Differentiation
The Protein Deacetylase SIRT3 Prevents Oxidative Stress-induced Keratinocyte Differentiation
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DOI：
10.1074/jbc.m113.472324
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发表时间：
2013-12-20
影响因子：
4.8
通讯作者：
Haigis, Marcia C.
中科院分区：
文献类型：
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作者：
Bause, Alexandra S.;Matsui, Mary S.;Haigis, Marcia C.
背景：SIRT3 在防止线粒体氧化应激方面发挥着重要作用。结果：角质形成细胞分化过程中氧化应激增加，SIRT3 可以通过减弱氧化应激来减少分化。结论：SIRT3 诱导的线粒体氧化应激下调会减弱角质形成细胞分化。意义：了解角质形成细胞分化的调节对于开发针对皮肤分化失调和衰老的新疗法至关重要。角质形成细胞分化是保护性皮肤屏障形成和维持的关键过程。活性氧稳态平衡失调可能在角质形成细胞分化中发挥作用。我们已经确定线粒体脱乙酰酶 SIRT3 是角质形成细胞中线粒体活性氧的关键调节剂。我们的研究表明，SIRT3 表达在角质形成细胞分化过程中下调，与线粒体超氧化物水平的增加一致。重要的是，角质形成细胞中SIRT3表达的丧失增加了超氧化物水平并促进了分化标记物的表达，而过度表达则降低了超氧化物水平并减少了分化标记物的表达。这些发现确定了 SIRT3 在通过降低氧化应激抑制表皮分化中的新作用。
Background: SIRT3 plays a major role in protecting against mitochondrial oxidative stress. Results: Oxidative stress increases during keratinocyte differentiation, and SIRT3 can decrease differentiation by attenuating oxidative stress. Conclusion: SIRT3-induced down-regulation of mitochondrial oxidative stress attenuates keratinocyte differentiation. Significance: Understanding the regulation of keratinocyte differentiation is crucial for developing new therapies against dysregulated skin differentiation and aging.Keratinocyte differentiation is a key process in the formation and maintenance of the protective skin barrier. Dysregulation in the balance of reactive oxygen species homeostasis may play a role in keratinocyte differentiation. We have identified the mitochondrial deacetylase SIRT3 as a key regulator of mitochondrial reactive oxygen species in keratinocytes. Our studies demonstrate that SIRT3 expression is down-regulated during keratinocyte differentiation, consistent with an increase in mitochondrial superoxide levels. Importantly, loss of SIRT3 expression in keratinocytes increased superoxide levels and promoted the expression of differentiation markers, whereas overexpression decreased superoxide levels and reduced the expression of differentiation markers. These findings identify a new role for SIRT3 in the suppression of epidermal differentiation via lowering oxidative stress.