Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline
Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline
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DOI：
10.1016/j.bbrc.2003.10.191
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发表时间：
2003-12-19
影响因子：
3.1
通讯作者：
Fujii, J
中科院分区：
文献类型：
--
作者：
Matsuki, S;Iuchi, Y;Fujii, J
生精细胞对热应激敏感并发生凋亡。尽管有多种因素似乎参与了凋亡过程。胞内信号传导途径的性质是不明确的。为了阐明这一过程，我们选择了一个简单的模型，将小鼠睾丸浸入42 ℃的热水中15分钟。TUNEL法检测DNA原位断裂。Western blotting检测到热处理的睾丸和42 ℃孵育1 h的生精细胞中细胞色素e释放到细胞质中，但支持细胞中没有。米诺环素是一种半合成四环素，已知可通过渗透血脑屏障到达大脑并抑制神经元细胞的凋亡。由于睾丸也有类似的屏障，米诺环素被视为抑制热应激诱导的细胞凋亡的可能药物。结果表明，米诺环素抑制释放细胞色素e从线粒体在体内和体外，并显着减少TUNEL阳性细胞的数量。这些结果表明，睾丸热应激触发细胞色素c从生精细胞线粒体中释放，导致细胞凋亡途径的激活。(C)2003年爱思唯尔公司All rights reserved.
Spermatogenic cells are susceptible to heat stress and undergo apoptosis. Although a variety of factors appear to be involved in the apoptotic process. the nature of the intracellular signaling pathway is ambiguous. To clarify the process, we chose a simple model in which testes of mice were exposed to mild heating by immersion in hot water at 42degreesC for 15min. In situ DNA fragmentation was detected by a TUNEL method. The release of cytochrome e into the cytoplasm was observed by Western blotting both in heat-treated testis and in isolated spermatogenic cells that had been incubated at 42degreesC for 1 h, but not in Sertoli cells. Minocycline, a semisynthetic tetracycline, is known to reach the brain by permeating the blood-brain barrier and suppresses apoptosis in neuronal cells. Since the testis also has a similar barrier, minocycline was examined as a possible agent to inhibit heat stress-induced apoptosis. The results indicate that minocycline suppressed the release of cytochrome e from mitochondria both in vivo and in vitro and significantly decreased the number of TUNEL-positive cells. These findings suggest that heat stress of testes triggers the release of cytochrome c from mitochondria in spermatogenic cells, leading to the activation of an apoptotic pathway. (C) 2003 Elsevier Inc. All rights reserved.