Midkine rescues Wilms' tumor cells from cisplatin-induced apoptosis: Regulation of Bcl-2 expression by midkine
Midkine rescues Wilms' tumor cells from cisplatin-induced apoptosis: Regulation of Bcl-2 expression by midkine
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DOI：
10.1093/oxfordjournals.jbchem.a022604
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发表时间：
2000-02-01
影响因子：
2.7
通讯作者：
Kadomatsu, K
中科院分区：
文献类型：
--
作者：
Qi, MS;Ikematsu, S;Kadomatsu, K
中期因子（MK）是一种肝素结合生长因子，参与多种生物学现象，例如神经元存活、癌发生和组织修复。MK主要在成年小鼠的肾脏中表达。在这项研究中，我们发现，在能够诱导可恢复的肾损伤和诱导细胞凋亡的剂量下，顺铂（CDDP）瞬时抑制小鼠肾脏中MK的表达。体外实验表明，CDDP抑制了体外培养的肾母细胞瘤细胞系G401的MK表达，并诱导其凋亡。外源性MK蛋白可部分挽救CDDP诱导的G401细胞凋亡，MK可剂量依赖性地增加G401细胞Bcl-2的表达，但对Bcl-x（L）的表达无影响，并可阻止CDDP引起的Bcl-2的减少。CDDP处理也可短暂抑制小鼠肾脏中Bcl-2的表达，其表达谱与MK相似。这些结果表明MK对损伤性损伤发挥细胞保护活性，推测至少部分是通过增强Bcl-2的表达。
Midkine (MK) is a heparin-binding growth factor involved in diverse biological phenomena, e.g. neuronal survival, carcinogenesis, and tissue repair. MK expression is detected mainly in the kidney in adult mice, In this study, we show that, at a dose that can induce recoverable renal damage and induce apoptosis, cisplatin (CDDP) transiently suppressed MK expression in mouse kidney. In vitro, CDDP suppressed MK expression and induced apoptosis in cultured G401 cells, a Wilms' tumor cell line, Exogenous MK protein partially rescued G401 cells ii om CDDP-induced apoptosis, MK enhanced the expression of Bcl-2, but not that of Bcl-x(L), in G401 cells in a dose-dependent manner, and it prevented the Bcl-2 reduction due to CDDP, Moreover, Bcl-2 expression in mouse kidney was also transiently suppressed by CDDP treatment, the expression profile being similar to that of MK, These results imply that MK exerts cytoprotective activity toward a damaging insult, presumably at least in part through enhancement of the expression of Bcl-2.