Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries

Liu, Haohao; Zhang, Xiaofeng; Zhang, Shenshen; Huang, Hui; Wu, Jinxia; Wang, Yueqin; Yuan, Long; Liu, Chuanrui; Zeng, Xin; Cheng, Xuemin; Zhuang, Donggang; Zhang, Huizhen

doi:10.3389/fphys.2018.01058

Cited by 41 publications

(16 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microcystin-leucine-arginine induces cytotoxicity via oxidative stress in many kinds of cells, including tissues of the ovary ( Li et al, 2008 ; Liu et al, 2018 ). To investigate whether MC-LR was inhibiting oocyte maturation via oxidative stress, we used DCFH staining to compare the ROS levels between control and MC-LR-exposed oocytes.…”

Section: Resultsmentioning

confidence: 99%

Vitamin C Protects Porcine Oocytes From Microcystin-LR Toxicity During Maturation

Zhang

Zhou

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Microcystin-leucine arginine (MC-LR) is the most toxic cyanotoxin found in water bodies. Microcystins are produced as secondary products of cyanobacteria metabolism. They have a stable structure, and can bioaccumulate in living organisms. Humans and livestock who drink fresh water containing MC-LR can be poisoned. However, few studies have reported the effects of MC-LR exposure on livestock or human reproduction. In this study, we used porcine oocytes as a model to explore the effects of MC-LR on oocyte maturation, and studied the impact of vitamin C (VC) administration on MC-LR-induced meiosis defects. Exposure to MC-LR significantly restricted cumulus cell expansion and decreased first polar body extrusion. Further studies showed that MC-LR exposure led to meiosis arrest by disturbing cytoskeleton dynamics with MC-LR exposed oocytes displaying aberrant spindle organization, low levels of acetylate α-tubulin, and disturbed actin polymerization. Additionally, MC-LR exposure impaired cytoplasmic maturation by inducing mitochondria dysfunction. Moreover, MC-LR also produced abnormal epigenetic modifications, and induced high levels of oxidative stress, caused DNA damage and early apoptosis. The administration of VC provided partial protection from all of the defects observed in oocytes exposed to MC-LR. These results demonstrate that MC-LR has a toxic effect on oocyte meiosis through mitochondrial dysfunction-induced ROS, DNA damage and early apoptosis. Supplementation of VC is able to protect against MC-LR-induced oocyte damage and represents a potential therapeutic strategy to improve the quality of MC-LR-exposed oocytes.

show abstract

Section: Resultsmentioning

confidence: 99%

Vitamin C Protects Porcine Oocytes From Microcystin-LR Toxicity During Maturation

Zhang

Zhou

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…The inhibition rate of cell proliferation was detected by CCK‐8 kit as described previously . In detail, 100 μL cell suspension was added to 96‐well plate with a minimum inoculum density of 1000 cells/well.…”

Section: Methodsmentioning

confidence: 99%

“…FITC of 5 μL and PI staining solution of 10 μL were added, which were detected by flow cytometry within 1 hour after the mixture was incubated for 15 minutes in the dark. The experimental protocol is reference to our previous research …”

Section: Methodsmentioning

confidence: 99%

“…The inhibition rate of cell proliferation was detected by CCK-8 kit as described previously. 30,31 In detail, 100 μL cell suspension was added to 96-well plate with a minimum inoculum density of 1000 cells/well. It was incubated at 37 C for 24 hours before and after adding 10 μL MC-LR of various concentrations to those wells.…”

Section: Inhibition Rate Of Cell Proliferationmentioning

confidence: 99%

See 1 more Smart Citation

p53‐Dependent pathway and the opening of mPTP mediate the apoptosis of co‐cultured Sertoli‐germ cells induced by microcystin‐LR

Liu

Huang

et al. 2019

Environmental Toxicology

Self Cite

View full text Add to dashboard Cite

Microcystin‐LR (MC‐LR), a potent endotoxin, can induce reproductive toxicity. In order to investigate the role and mechanisms of apoptosis (p53‐dependent and mitochondrial pathways) of germ cells induced by MC‐LR, the co‐cultured primary Sertoli‐germ cells from Sprague‐Dawley rats were used for the experiments. Expression levels of proteins, genes, and mitochondrial membrane potential (MMP) were obtained after exposing co‐cultured Sertoli‐germ cells to MC‐LR with or without the addition of the p53 inhibitor, pifithrin‐α (PFT‐α), and MMP inhibitor, cyclosporin A (CsA). Results indicated that MC‐LR could activate p53‐dependent pathway‐associated proteins in Sertoli‐germ cells, leading to a decrease in MMP (indicating the opening of mitochondrial permeability transition pore [mPTP] and the release of Cytochrome‐c [Cyt‐c]) from the mitochondria into the cytoplasm and eventually the induction of apoptosis. PFT‐α inhibited the expression ofp53, ameliorated the MMP of the co‐cultured Sertoli‐germ cells, and prevented the release of Cyt‐c from the mitochondria into the cytoplasm, which reduces the occurrence of apoptosis. Similarly, the decreased release of Cyt‐c from the mitochondria into the cytoplasm and the declined level of apoptosis in Sertoli‐germ cells induced by MC‐LR were observed after the addition of CsA. These results indicated that the apoptosis of the co‐cultured Sertoli‐germ cells induced by MC‐LR was mediated by the p53‐dependent pathway, with the involvement of the opening of mPTP.

show abstract

“…3.7. VC decreases oxidative stress and alleviates DNA damage in MC-LR -exposed oocytes MC-LR induces cytotoxicity via oxidative stress in many kinds of cells, including tissues of the ovary [20,35]. To investigate whether MC-LR was inhibiting oocyte maturation via oxidative stress, we used DCFH staining to compare the ROS levels between control and MC-LR-exposed oocytes.…”

Section: Vitamin C Restores Abnormal Epigenetic Alterations In Mc-lrmentioning

confidence: 99%

Vitamin C protects porcine oocytes from microcystin-LR toxicity during maturation

Zhang

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Microcystin-leucine arginine (MC-LR) is the most toxic cyanotoxin found in water bodies. Microcystins are produced as secondary products of cyanobacteria metabolism. They have a stable structure, and can bioaccumulate in living organisms. Humans and livestock who drink fresh water containing MC-LR can be poisoned. However, few studies have reported the effects of MC-LR exposure on livestock or human reproduction.Results: We used porcine oocytes as the model to explore the effects of MC-LR on oocyte maturation, and studied the impact of vitamin C (VC) administration on MC-LR‐induced meiosis defects. Exposure to MC-LR significantly restricted cumulus cell expansion and decreased first polar body extrusion. Further studies showed that MC-LR exposure led to meiosis arrest by disturbing cytoskeleton dynamics with MC-LR exposed oocytes displaying aberrant spindle organization, low levels of acetylate α‐tubulin, and disturbed actin polymerization. Additionally, MC-LR exposure impaired cytoplasmic maturation by disturbing mitochondria distribution. Moreover, MC-LR also produced abnormal epigenetic modifications, and induced high levels of oxidative stress and DNA damage. The administration of VC provided partial protection from all of the defects observed in oocytes exposed to MC-LR. Conclusions: These results demonstrate that MC-LR has a toxic effect on oocyte meiosis through the generation of excessive ROS levels and DNA damage. Supplementation of VC was able to protect against MC-LR-induced oocyte damage and represents a potential therapeutic strategy to improve the quality of MC-LR-exposed oocytes.

show abstract

Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6 Mice Ovaries

Cited by 41 publications

References 63 publications

Vitamin C Protects Porcine Oocytes From Microcystin-LR Toxicity During Maturation

Vitamin C Protects Porcine Oocytes From Microcystin-LR Toxicity During Maturation

p53‐Dependent pathway and the opening of mPTP mediate the apoptosis of co‐cultured Sertoli‐germ cells induced by microcystin‐LR

Vitamin C protects porcine oocytes from microcystin-LR toxicity during maturation

Contact Info

Product

Resources

About