Caspase-3 in the rat ovary: Localization and possible role in follicular atresia and luteal regression
Caspase-3 in the rat ovary: Localization and possible role in follicular atresia and luteal regression
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DOI：
10.1095/biolreprod58.6.1533
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发表时间：
1998-06-01
影响因子：
3.6
通讯作者：
Tsang, BK
中科院分区：
文献类型：
--
作者：
Boone, DL;Tsang, BK
细胞凋亡是卵巢卵泡闭锁和黄体退化的细胞机制，是由半胱氨酸天冬氨酸特异性蛋白酶（caspases）的蛋白水解级联激活触发的。细胞死亡的主要下游效应物是caspase-3，但对该酶在卵巢凋亡中的作用或调控知之甚少。caspase-3的两种底物，肌动蛋白和聚（adp -核糖）聚合酶（PARP）是DNA酶I的抑制剂，DNA酶I是负责卵巢凋亡DNA降解的内切酶。因此，我们研究了大鼠卵巢卵泡闭锁（促性腺激素停用）和黄体退化（前列腺素F-2 α诱导）过程中肌动蛋白和PARP的蛋白水解裂解以及caspase-3的定位。细胞凋亡DNA降解在卵泡闭锁和黄体退行期间均明显，但PARP和肌动蛋白的裂解仅在黄体退行期间观察到。Caspase-3定位于健康黄体（CL）的黄体细胞和卵泡，而不定位于健康卵泡的颗粒细胞。然而，在闭锁卵泡的颗粒细胞中，caspase-3免疫染色明显，其模式与颗粒细胞死亡的定位相似。正常细胞与凋亡细胞在caspase-3染色的分布和强度上无差异。这些结果表明，在卵巢细胞凋亡过程中，肌动蛋白和PARP的裂解并不是激活凋亡DNA降解的必要条件。此外，在闭锁而非健康的卵泡颗粒细胞中存在caspase-3，表明该酶的表达受促性腺激素的调节，并可能作为颗粒细胞凋亡过程的一部分而上调。
Apoptosis, the cellular mechanism of ovarian follicular atresia and luteal regression, is triggered by the activation of a proteolytic cascade of cysteine aspartate-specific proteases (caspases). The principle downstream effector of cell death is caspase-3, but little is known about the role or regulation of this enzyme in ovarian apoptosis. Two substrates of caspase-3, actin and poly(ADP-ribose) polymerase (PARP), are inhibitors of DNase I, which is the endonuclease responsible for ovarian apoptotic DNA degradation. We therefore investigated the proteolytic cleavage of actin and PARP as well as the localization of caspase-3 during follicular atresia (induced by gonadotropin withdrawal) and luteal regression (induced by prostaglandin F-2 alpha) in the rat ovary. Apoptotic DNA degradation was evident during both follicular atresia and luteal regression, but cleavage of PARP and actin was observed only during luteal regression. Caspase-3 was localized in luteal cells of healthy corpora lutea (CL) and in theca, but not in granulosa cells of healthy follicles. However, caspase-3 immunostaining was evident in granulosa cells of atretic follicles in a pattern similar to that of the localization of granulosa cell death. There was no difference between healthy and apoptotic CL in the distribution or intensity of caspase-3 staining. These results demonstrate that the cleavage of actin and PARP are not necessary for activation of apoptotic DNA degradation during ovarian apoptosis. In addition, the presence of caspase-3 in granulosa cells of atretic, but not healthy, follicles suggests that the expression of this enzyme is regulated by gonadotropin and may be up-regulated as part of the apoptotic process in granulosa cells.