Glycine Ameliorates Endoplasmic Reticulum Stress Induced by Thapsigargin in Porcine Oocytes.
Glycine Ameliorates Endoplasmic Reticulum Stress Induced by Thapsigargin in Porcine Oocytes.
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甘氨酸改善毒胡萝卜素诱导的猪卵母细胞内质网应激
DOI：
10.3389/fcell.2021.733860
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Yu S;Gao L;Zhang C;Wang Y;Lan H;Chu Q;Li S;Zheng X
内质网（ER）是一种多功能的细胞器，在雌性哺乳动物的生殖过程中起着重要作用。内质网和线粒体相互作用，通过维持细胞内钙稳态来维持细胞的正常功能。研究表明，甘氨酸（Gly）可以调节细胞内游离钙浓度（[Ca 2 +]i），增强线粒体功能，促进卵母细胞体外成熟。Gly对卵母细胞体外成熟过程中ER功能的影响尚不清楚。本研究采用毒胡萝卜素（thapsigargin，TG）诱导内质网应激模型，探讨Gly是否能逆转TG诱导的内质网应激，以及Gly是否与钙调节有关。结果表明，添加Gly可以改善TG诱导的ER应激引起的平均卵丘直径、第一极体排泄率、卵裂率和囊胚率的下降。补充Gly可以通过显着提高ER水平并显着下调ER应激相关基因（Xbp 1、ATF 4和ATF 6）的表达来减轻TG诱导的ER应激。此外，Gly还能显著降低TG诱导的猪卵母细胞活性氧（ROS）水平的升高和线粒体膜电位（Δ Km）的降低，改善线粒体功能。此外，Gly还能降低TG处理的猪卵母细胞[Ca ~（2+）]i和线粒体Ca ~（2+）（[Ca ~（2+）]m）水平，恢复ER Ca ~（2+）（[Ca ~（2+）]ER）水平。此外，我们还发现[Ca ~（2+）]i升高可能是由于三磷酸肌醇受体（IP 3R 1）和电压依赖性阴离子通道1（VDAC 1）的分布和表达发生变化所致，而Gly可使IP 3R 1和VDAC 1的分布和表达恢复到正常水平。TG组细胞凋亡相关指标Caspase 3活性、Annexin-V及Bax、Cyto C、Caspase 3基因表达均显著升高，但加入Gly后可恢复。本研究结果表明，Gly可以改善TG处理后猪卵母细胞的内质网应激和细胞凋亡，进一步提高猪卵母细胞的体外发育潜能。
The endoplasmic reticulum (ER) is a multifunctional organelle in the cytoplasm that plays important roles in female mammalian reproduction. The endoplasmic reticulum and mitochondria interact to maintain the normal function of cells by maintaining intracellular calcium homeostasis. As proven by previous research, glycine (Gly) can regulate the intracellular free calcium concentration ([Ca2+]i) and enhance mitochondrial function to improve oocyte maturation in vitro. The effect of Gly on ER function during oocyte in vitro maturation (IVM) is not clear. In this study, we induced an ER stress model with thapsigargin (TG) to explore whether Gly can reverse the ER stress induced by TG treatment and whether it is associated with calcium regulation. The results showed that the addition of Gly could improve the decrease in the average cumulus diameter, the first polar body excretion rate caused by TG-induced ER stress, the cleavage rate and the blastocyst rate. Gly supplementation could reduce the ER stress induced by TG by significantly improving the ER levels and significantly downregulating the expression of genes related to ER stress (Xbp1, ATF4, and ATF6). Moreover, Gly also significantly alleviated the increase in reactive oxygen species (ROS) levels and the decrease in mitochondrial membrane potential (ΔΨ m) to improve mitochondrial function in porcine oocytes exposed to TG. Furthermore, Gly reduced the [Ca2+]i and mitochondrial Ca2+ ([Ca2+]m) levels and restored the ER Ca2+ ([Ca2+]ER) levels in TG-exposed porcine oocytes. Moreover, we found that the increase in [Ca2+]i may be caused by changes in the distribution and expression of inositol 1,4,5-triphosphate receptor (IP3R1) and voltage-dependent anion channel 1 (VDAC1), while Gly can restore the distribution and expression of IP3R1 and VDAC1 to normal levels. Apoptosis-related indexes (Caspase 3 activity and Annexin-V) and gene expression Bax, Cyto C, and Caspase 3) were significantly increased in the TG group, but they could be restored by adding Gly. Our results suggest that Gly can ameliorate ER stress and apoptosis in TG-exposed porcine oocytes and can further enhance the developmental potential of porcine oocytes in vitro.
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影响因子：
7.8
作者：
Hitomi, Junichi;Katayama, Taiichi;Eguchi, Yutaka;Kudo, Takashi;Taniguchi, Manabu;Koyama, Yoshihisa;Manabe, Takayuki;Yamagishi, Satoru;Bando, Yoshio;Imaizumi, Kazunori;Tsujimoto, Yoshihide;Tohyama, Masaya
通讯作者：
Tohyama, Masaya
影响因子：
1.8
作者：
Liang SL;Zhao QJ;Li XC;Jin YP;Wang YP;Su XH;Guan WJ;Ma YH
通讯作者：
Ma YH
影响因子：
5.2
作者：
Jheng JR;Ho JY;Horng JT
通讯作者：
Horng JT
影响因子：
2
作者：
de Almeida Barros, Fabiana Dakkach;Adona, Paulo Roberto;Michelette Damiao, Bruno Cesar
通讯作者：
Michelette Damiao, Bruno Cesar
影响因子：
82.9
作者：
Iwawaki, T;Akai, R;Miura, M
通讯作者：
Miura, M