Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries
Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide intracellular toxin released by cyanobacteria that exhibits strong reproductive toxicity. However, little is known about its biotoxicity to the female reproductive system. The present study investigates unexplored molecular pathways by wh...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.01058/full |
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| author | Haohao Liu Xiaofeng Zhang Shenshen Zhang Hui Huang Jinxia Wu Yueqin Wang Le Yuan Chuanrui Liu Xin Zeng Xuemin Cheng Donggang Zhuang Huizhen Zhang |
| author_facet | Haohao Liu Xiaofeng Zhang Shenshen Zhang Hui Huang Jinxia Wu Yueqin Wang Le Yuan Chuanrui Liu Xin Zeng Xuemin Cheng Donggang Zhuang Huizhen Zhang |
| author_sort | Haohao Liu |
| collection | DOAJ |
| description | Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide intracellular toxin released by cyanobacteria that exhibits strong reproductive toxicity. However, little is known about its biotoxicity to the female reproductive system. The present study investigates unexplored molecular pathways by which oxidative stress acts on MC-LR-induced endoplasmic reticulum stress (ERs) and autophagy. In the present study, immortalized murine ovarian granular cells (KK-1 cells) were exposed to 8.5, 17, and 34 μg/mL (IC50) of MC-LR with or without N-acetyl-l-cysteine (NAC, 10 mM) for 24 h, and C57BL/6 mice were treated with 12.5, 25.0, and 40.0 μg/kg⋅bw of MC-LR with or without NAC (200 mg/kg⋅bw) for 14 days. The results revealed that MC-LR could induce cells apoptosis and morphologic changes in ovarian tissues, induce oxidative stress by stimulating the generation of reactive oxygen species (ROS), destroying antioxidant capacity, and subsequently trigger ERs and autophagy by inducing the hyper-expression of ATG12, ATG5, ATG16, EIF2α (phosphorylated at S51), CHOP, XBP1, GRP78, Beclin1, and PERK (Thr980). Furthermore, NAC pretreatment partly inhibited MC-LR-induced ERs and autophagy via the PERK/ATG12 and XBP1/Beclin1 pathways. These results suggest that oxidative stress mediated MC-LR-induced ERs and autophagy in KK-1 cells and C57BL/6 mice ovaries. Therefore, oxidative stress plays an important role in female toxicity induced by MC-LR. |
| first_indexed | 2024-12-23T04:55:08Z |
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| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-23T04:55:08Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj.art-0839b946f6b54a219fe4c4d240dd1c0c2022-12-21T17:59:22ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-08-01910.3389/fphys.2018.01058365063Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice OvariesHaohao LiuXiaofeng ZhangShenshen ZhangHui HuangJinxia WuYueqin WangLe YuanChuanrui LiuXin ZengXuemin ChengDonggang ZhuangHuizhen ZhangMicrocystin-leucine arginine (MC-LR) is a cyclic heptapeptide intracellular toxin released by cyanobacteria that exhibits strong reproductive toxicity. However, little is known about its biotoxicity to the female reproductive system. The present study investigates unexplored molecular pathways by which oxidative stress acts on MC-LR-induced endoplasmic reticulum stress (ERs) and autophagy. In the present study, immortalized murine ovarian granular cells (KK-1 cells) were exposed to 8.5, 17, and 34 μg/mL (IC50) of MC-LR with or without N-acetyl-l-cysteine (NAC, 10 mM) for 24 h, and C57BL/6 mice were treated with 12.5, 25.0, and 40.0 μg/kg⋅bw of MC-LR with or without NAC (200 mg/kg⋅bw) for 14 days. The results revealed that MC-LR could induce cells apoptosis and morphologic changes in ovarian tissues, induce oxidative stress by stimulating the generation of reactive oxygen species (ROS), destroying antioxidant capacity, and subsequently trigger ERs and autophagy by inducing the hyper-expression of ATG12, ATG5, ATG16, EIF2α (phosphorylated at S51), CHOP, XBP1, GRP78, Beclin1, and PERK (Thr980). Furthermore, NAC pretreatment partly inhibited MC-LR-induced ERs and autophagy via the PERK/ATG12 and XBP1/Beclin1 pathways. These results suggest that oxidative stress mediated MC-LR-induced ERs and autophagy in KK-1 cells and C57BL/6 mice ovaries. Therefore, oxidative stress plays an important role in female toxicity induced by MC-LR.https://www.frontiersin.org/article/10.3389/fphys.2018.01058/fullmicrocystin-leucine arginine (MC-LR)oxidative stressendoplasmic reticulum stress (ERs)autophagyN-acetyl-l-cysteine (NAC) |
| spellingShingle | Haohao Liu Xiaofeng Zhang Shenshen Zhang Hui Huang Jinxia Wu Yueqin Wang Le Yuan Chuanrui Liu Xin Zeng Xuemin Cheng Donggang Zhuang Huizhen Zhang Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries Frontiers in Physiology microcystin-leucine arginine (MC-LR) oxidative stress endoplasmic reticulum stress (ERs) autophagy N-acetyl-l-cysteine (NAC) |
| title | Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries |
| title_full | Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries |
| title_fullStr | Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries |
| title_full_unstemmed | Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries |
| title_short | Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries |
| title_sort | oxidative stress mediates microcystin lr induced endoplasmic reticulum stress and autophagy in kk 1 cells and c57bl 6 mice ovaries |
| topic | microcystin-leucine arginine (MC-LR) oxidative stress endoplasmic reticulum stress (ERs) autophagy N-acetyl-l-cysteine (NAC) |
| url | https://www.frontiersin.org/article/10.3389/fphys.2018.01058/full |
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