Age- and oxidative stress-induced DNA damage in Drosophila intestinal stem cells as marked by Gamma-H2AX

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• 作者：Joung-Sun Park^a ; ¹ ; Shin-Hae Lee^a ; ¹ ; Hyun-Jin Na^a ; Jung-Hoon Pyo^a ; Young-Shin Kim^b ; Mi-Ae Yoo^a ; ^{mayoo@pusan.ac.kr}
• 关键词：Drosophila ; Intestinal stem cell ; Aging ; DNA damage ; 纬H2AX ; 纬H2AvD
• 刊名：Experimental Gerontology
• 出版年：2012
• 期刊代码：99_05315565
• 类别：med
• 出版时间：May, 2012
• 卷：47
• 期：5
• 页码：401-405
• 文件大小：1082 K

摘要

A decline in stem cell function is considered as a major cause of tissue atrophy, organ-system failure, cancer development and aging process. For a better understanding of the mechanism underlying age-related decline of stem cell function, characterization of aged stem cells is required. DNA damage induces epigenetic modifications that are associated with cell dysfunction. In mammals, 纬H2AX has been shown as DNA damage marker and an adaptor for recruiting chromatin modifying factors. In current study, utilizing a well-accepted Drosophila midgut model for stem-cell biology, we demonstrated aging- and oxidative stress-related accumulation of 纬H2AvD foci, analogous to mammal 纬H2AX, in Drosophila intestinal stem cells (ISCs), and obtained evidence that the changes in 纬H2AvD is closely associated with 纬-ray-induced DNA damage in ISCs and age-related accumulation of 8-oxo-2鈥?deoxyguanosine. The significance of our study is to document the first direct evidence for the accumulation of age-related DNA-damage in ISCs, and to show 纬H2AvD as a useful biomarker in exploring the molecular mechanisms underlying stem cell aging in the Drosophila midgut.