Glutathione deficiency sensitizes cultured embryonic mouse ovaries to benzo[a]pyrene-induced germ cell apoptosis.
Glutathione deficiency sensitizes cultured embryonic mouse ovaries to benzo[a]pyrene-induced germ cell apoptosis.
复制标题
DOI：
10.1016/j.taap.2018.05.024
复制
发表时间：
2018-08-01
影响因子：
3.8
通讯作者：
Luderer U
中科院分区：
文献类型：
--
作者：
Lim J;Luderer U
缺乏谷氨酸半胱氨酸连接酶（Gclm）修饰亚基的小鼠，谷胱甘肽（GSH）合成的限速酶，组织GSH减少。我们先前表明，Gclm −/−胚胎对多环芳烃苯并[a]芘（BaP）的产前体内卵巢毒性的敏感性高于Gclm +/+同窝仔。我们还发现，苯并（a）芘诱导的野生型胚胎卵巢生殖细胞死亡是半胱天冬酶依赖的。在这里，我们假设，GSH缺乏增加培养的胚胎卵巢的敏感性BaP诱导的生殖细胞死亡。13.5将所有Gclm基因型的胚胎卵巢立即固定或在补充有DMSO载体或500 ng/ml BaP的培养基中培养24小时。活化的caspase-3阳性生殖细胞的百分比在组间差异显著。在每种基因型中，DMSO和BaP处理组与未培养组相比，生殖细胞caspase-3活化增加。与DMSO相比，BaP处理的Gclm +/−卵巢的caspase-3活化显著增加，而与DMSO相比，BaP处理的Gclm −/−卵巢的caspase-3活化增加不显著。BaP处理对24小时的生殖细胞数量没有统计学显著影响，与我们先前在野生型卵巢中的观察结果一致，但两个培养组中的Gclm −/−卵巢的生殖细胞数量低于Gclm +/+卵巢。在脂质过氧化和生殖细胞增殖方面，各组之间没有统计学显著的BaP治疗或基因型相关差异。这些数据表明，Gclm杂合或纯合缺失敏感的胚胎卵巢BaP和组织培养诱导的生殖细胞凋亡。
Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in glutathione (GSH) synthesis, have decreased tissue GSH. We previously showed that Gclm−/− embryos have increased sensitivity to the prenatal in vivo ovarian toxicity of the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) compared with Gclm+/+ littermates. We also showed that BaP-induced germ cell death in cultured wild type embryonic ovaries is caspase-dependent. Here, we hypothesized that GSH deficiency increases sensitivity of cultured embryonic ovaries to BaP-induced germ cell death. 13.5 days post coitum (dpc) embryonic ovaries of all Gclm genotypes were fixed immediately or cultured for 24h in media supplemented with DMSO vehicle or 500 ng/ml BaP. The percentage of activated caspase-3 positive germ cells varied significantly among groups. Within each genotype, DMSO and BaP-treated groups had increased germ cell caspase-3 activation compared to uncultured. Gclm+/− ovaries had significantly increased caspase-3 activation with BaP treatment compared to DMSO, and caspase-3 activation increased non-significantly in Gclm−/− ovaries treated with BaP compared to DMSO. There was no statistically significant effect of BaP treatment on germ cell numbers at 24h, consistent with our prior observations in wild type ovaries, but Gclm−/− ovaries in both cultured groups had lower germ cell numbers than Gclm+/+ ovaries. There were no statistically significant BaP-treatment or genotype-related differences among groups in lipid peroxidation and germ cell proliferation. These data indicate that Gclm heterozygous or homozygous deletion sensitizes embryonic ovaries to BaP- and tissue culture-induced germ cell apoptosis.
登录
查看更多内容
影响因子：
3.5
作者：
Halliwell, B
通讯作者：
Halliwell, B
影响因子：
11.8
作者：
Luderer U;Christensen F;Johnson WO;She J;Ip HS;Zhou J;Alvaran J;Krieg EF Jr;Kesner JS
通讯作者：
Kesner JS
影响因子：
3.9
作者：
GARDINER, CS;REED, DJ
通讯作者：
REED, DJ
影响因子：
2.5
作者：
Díaz, D;Krejsa, CM;Kavanagh, TJ
通讯作者：
Kavanagh, TJ
DOI：
10.1006/faat.1996.0187
发表时间：
1996-12-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
Miller, MS;Juchau, MR;Raucy, JL
通讯作者：
Raucy, JL