Age-associated changes in the subcellular localization of phosphorylated p38 MAPK in human granulosa cells
Age-associated changes in the subcellular localization of phosphorylated p38 MAPK in human granulosa cells
复制标题
DOI：
10.1093/molehr/gaq076
复制
发表时间：
2010-12-01
影响因子：
4
通讯作者：
Takahashi, Yuji
中科院分区：
文献类型：
--
作者：
Ito, Megumu;Miyado, Kenji;Takahashi, Yuji
P38MAPK(P38)在衰老和生殖生理中起着关键作用。然而，p38在女性生殖衰老中的作用尚不确定。为了更好地了解p38在年龄相关性生殖失败中的作用，我们研究了磷酸化p38在人颗粒细胞中的表达和亚细胞定位。在老年受试者的细胞中，p38的激活程度是年轻受试者的7倍。在用过氧化氢(H_2O_2)处理的人颗粒样KGN细胞中也得到了类似的结果。有趣的是，在老年细胞中，p38在细胞核中被检测到的频率低于年轻细胞(年轻细胞：58.6%；老年细胞：29.8%，P<；0.01)。同样，经过氧化氢处理后，KGN细胞中磷酸化p38的胞质定位也被观察到。N-乙酰半胱氨酸和SB203580可阻断H_2O_2处理的KGN细胞中p38的激活和胞质定位。尽管p38激活剂FSH和肿瘤坏死因子-α在KGN细胞中诱导了类似的磷酸化p38的定位，但p38的表达和定位模式与老年颗粒细胞和经H_2O_2处理的KGN细胞不同。这些结果表明，p38在老年颗粒细胞中的特征定位是由氧化应激诱导的。
p38 MAPK (p38) plays pivotal roles in aging and reproductive physiology. Nevertheless, involvement of p38 in female reproductive aging is uncertain. To improve knowledge of the role of p38 in age-associated reproductive failure, the expression and subcellular localization of phosphorylated p38 was investigated in human granulosa cells. p38 was 7-fold more activated in cells from older subjects than in those from younger subjects. Similar results were obtained in human granulosa-like KGN cells treated with hydrogen peroxide (H2O2). Interestingly, phosphorylated p38 was detected in the nucleus less frequently in older cells than in younger cells (Younger: 58.6%; Older: 29.8%, P < 0.01). Similarly cytoplasmic localization of phosphorylated p38 in KGN cells was observed after treatment with H2O2. The activation and cytoplasmic localization of p38 in H2O2-treated KGN cells were blocked by N-acetylcysteine and SB203580. Although the p38 activators, FSH and tumor necrosis factor-alpha, induced a similar localization of phosphorylated p38 in KGN cells, the expression and localization patterns of p38 were distinct from those in older granulosa cells and H2O2-treated KGN cells. These results indicate that the characteristic localization of p38 in older granulosa cells is induced by oxidative stress.