Involvement of mitochondria in oxidative stress-induced cell death in mouse zygotes
Involvement of mitochondria in oxidative stress-induced cell death in mouse zygotes
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DOI：
10.1095/biolreprod62.6.1745
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发表时间：
2000-06-01
影响因子：
3.6
通讯作者：
Keefe, DL
中科院分区：
文献类型：
--
作者：
Liu, L;Trimarchi, JR;Keefe, DL
衰老过程中活性氧的积累导致许多细胞类型中的程序性细胞死亡（PCD），但尚未在哺乳动物受精卵中探索，其中线粒体是“不成熟的”，与体细胞中的“成熟”线粒体相反。我们的特点是PCD在小鼠受精卵诱导无论是密集的（1毫米为1.5小时）或温和的（200 μ M为15分钟）过氧化氢（H2 O2）处理。强化处理后不久，受精卵显示PCD，典型的细胞收缩，细胞色素c从线粒体释放，半胱天冬酶激活，然后在浓缩的原核末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色。另一方面，温和处理后，受精卵发育停滞，在48小时内既没有细胞色素c释放，也没有半胱天冬酶激活;直到72小时，46%的受精卵表现出TU NEL染色，88%的受精卵失去质膜完整性。有趣的是，轻度氧化处理诱导线粒体膜电位下降和线粒体基质破坏。总而言之，这些结果表明H2 O2引起的氧化应激诱导小鼠受精卵的PCD，并且线粒体参与了氧化应激诱导的PCD的早期阶段。此外，线粒体功能障碍也可能导致细胞周期停滞，随后由轻度氧化应激引发细胞死亡。
Accumulation of reactive oxygen species during aging leads to programmed cell death (PCD) in many cell types but has not been explored in mammalian fertilized eggs, in which mitochondria are "immature," in contrast to "mature" mitochondria in somatic cells. We characterized PCD in mouse zygotes induced by either intensive (1 mM for 1.5 h) or mild (200 mu M for 15 min) hydrogen peroxide (H2O2) treatment. Shortly after intensive treatment, zygotes displayed PCD, typified by cell shrinkage, cytochrome c release from mitochondria, and caspase activation, then terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in condensed pronuclei. On the other hand, after mild treatment, zygotes arrested developmentally and showed neither cytochrome c release nor caspase activation over 48 h; until 72 h, 46% zygotes exhibited TU NEL staining, and 88% of zygotes lost plasma membrane integrity. Interestingly, mild oxidative treatment induced a decline in mitochondrial membrane potential and disruption of the mitochondrial matrix. Taken together, these results suggest that oxidative stress caused by H2O2 induces PCD in mouse zygotes and that mitochondria are involved in the early phase of oxidative stress-induced PCD. Furthermore, mitochondrial malfunction also may contribute to cell cycle arrest, followed by cell death, triggered by mild oxidative stress.