Mitochondrial and endoplasmic reticulum pathways involved in microcystin-LR-induced apoptosis of the testes of male frog (Rana nigromaculata) in vivo
•MCLR can induce apoptosis on testes of Rana nigromaculata.•1μg/L MCLR (the drinking water standard level) has ecological risks on frogs.•MCLR induces frog testes apoptosis via oxidative stress.•MCLR-induced apoptosis on frog testes is associated with mitochondrial pathway.•Endoplasmic reticulum pat...
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Published in | Journal of hazardous materials Vol. 252-253; pp. 382 - 389 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier B.V
15.05.2013
Elsevier |
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Abstract | •MCLR can induce apoptosis on testes of Rana nigromaculata.•1μg/L MCLR (the drinking water standard level) has ecological risks on frogs.•MCLR induces frog testes apoptosis via oxidative stress.•MCLR-induced apoptosis on frog testes is associated with mitochondrial pathway.•Endoplasmic reticulum pathway is involved in MCLR-induced apoptosis on frog testes.
Previous studies have shown that toxins produced by toxic cyanobacterial blooms are hazardous materials. In the present study, 1μg/L microcystin-LR (MC-LR) was observed to induce apoptosis in the testes of male Rana nigromaculata via the mitochondrial and endoplasmic reticulum (ER) pathways at exposure times ranging from 7 d to 14 d. The results showed that reactive oxygen species production and malondialdehyde content were positively correlated with exposure time. Antioxidant enzyme contents, such as reduced glutathione and glutathione peroxidase rapidly decreased, implying that the defense system of the testes induces oxidative damage. MC-LR significantly stimulated the release of cytochrome c in the testes, thereby improving the protein expressions of Bax and caspases-3, 8, and 9 (p<0.01) and inhibiting the protein expression of Bcl-2 with prolonged exposure (p<0.01). Ultrastructural observations showed distention of the mitochondria and endoplasmic reticulum and deformation of the nucleolus. Moreover, prolonged exposure times strengthened and weakened the relative expression levels of C/EBP homologous protein and GRP78, respectively. These results indicate that MC-LR-induced apoptosis of the testes in male frogs in vivo may occur through the mitochondrial and ER pathways. It also further proves our previous findings that MC-LR can induce toxicity in the male reproductive system of R. nigromaculata in vitro. The findings show that MC-LR is highly hazardous to frogs and that the accepted drinking water limit of 1μg/L MC-LR exerts significant toxicity to amphibians. |
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AbstractList | Previous studies have shown that toxins produced by toxic cyanobacterial blooms are hazardous materials. In the present study, 1 μg/L microcystin-LR (MC-LR) was observed to induce apoptosis in the testes of male Rana nigromaculata via the mitochondrial and endoplasmic reticulum (ER) pathways at exposure times ranging from 7 d to 14 d. The results showed that reactive oxygen species production and malondialdehyde content were positively correlated with exposure time. Antioxidant enzyme contents, such as reduced glutathione and glutathione peroxidase rapidly decreased, implying that the defense system of the testes induces oxidative damage. MC-LR significantly stimulated the release of cytochrome c in the testes, thereby improving the protein expressions of Bax and caspases-3, 8, and 9 (p<0.01) and inhibiting the protein expression of Bcl-2 with prolonged exposure (p<0.01). Ultrastructural observations showed distention of the mitochondria and endoplasmic reticulum and deformation of the nucleolus. Moreover, prolonged exposure times strengthened and weakened the relative expression levels of C/EBP homologous protein and GRP78, respectively. These results indicate that MC-LR-induced apoptosis of the testes in male frogs in vivo may occur through the mitochondrial and ER pathways. It also further proves our previous findings that MC-LR can induce toxicity in the male reproductive system of R. nigromaculata in vitro. The findings show that MC-LR is highly hazardous to frogs and that the accepted drinking water limit of 1 μg/L MC-LR exerts significant toxicity to amphibians. •MCLR can induce apoptosis on testes of Rana nigromaculata.•1μg/L MCLR (the drinking water standard level) has ecological risks on frogs.•MCLR induces frog testes apoptosis via oxidative stress.•MCLR-induced apoptosis on frog testes is associated with mitochondrial pathway.•Endoplasmic reticulum pathway is involved in MCLR-induced apoptosis on frog testes. Previous studies have shown that toxins produced by toxic cyanobacterial blooms are hazardous materials. In the present study, 1μg/L microcystin-LR (MC-LR) was observed to induce apoptosis in the testes of male Rana nigromaculata via the mitochondrial and endoplasmic reticulum (ER) pathways at exposure times ranging from 7 d to 14 d. The results showed that reactive oxygen species production and malondialdehyde content were positively correlated with exposure time. Antioxidant enzyme contents, such as reduced glutathione and glutathione peroxidase rapidly decreased, implying that the defense system of the testes induces oxidative damage. MC-LR significantly stimulated the release of cytochrome c in the testes, thereby improving the protein expressions of Bax and caspases-3, 8, and 9 (p<0.01) and inhibiting the protein expression of Bcl-2 with prolonged exposure (p<0.01). Ultrastructural observations showed distention of the mitochondria and endoplasmic reticulum and deformation of the nucleolus. Moreover, prolonged exposure times strengthened and weakened the relative expression levels of C/EBP homologous protein and GRP78, respectively. These results indicate that MC-LR-induced apoptosis of the testes in male frogs in vivo may occur through the mitochondrial and ER pathways. It also further proves our previous findings that MC-LR can induce toxicity in the male reproductive system of R. nigromaculata in vitro. The findings show that MC-LR is highly hazardous to frogs and that the accepted drinking water limit of 1μg/L MC-LR exerts significant toxicity to amphibians. Previous studies have shown that toxins produced by toxic cyanobacterial blooms are hazardous materials. In the present study, 1 μg/L microcystin-LR (MC-LR) was observed to induce apoptosis in the testes of male Rana nigromaculata via the mitochondrial and endoplasmic reticulum (ER) pathways at exposure times ranging from 7 d to 14 d. The results showed that reactive oxygen species production and malondialdehyde content were positively correlated with exposure time. Antioxidant enzyme contents, such as reduced glutathione and glutathione peroxidase rapidly decreased, implying that the defense system of the testes induces oxidative damage. MC-LR significantly stimulated the release of cytochrome c in the testes, thereby improving the protein expressions of Bax and caspases-3, 8, and 9 (p<0.01) and inhibiting the protein expression of Bcl-2 with prolonged exposure (p<0.01). Ultrastructural observations showed distention of the mitochondria and endoplasmic reticulum and deformation of the nucleolus. Moreover, prolonged exposure times strengthened and weakened the relative expression levels of C/EBP homologous protein and GRP78, respectively. These results indicate that MC-LR-induced apoptosis of the testes in male frogs in vivo may occur through the mitochondrial and ER pathways. It also further proves our previous findings that MC-LR can induce toxicity in the male reproductive system of R. nigromaculata in vitro. The findings show that MC-LR is highly hazardous to frogs and that the accepted drinking water limit of 1 μg/L MC-LR exerts significant toxicity to amphibians. |
Author | Zhang, Hangjun Wu, Yingzhu Zhang, Yue Shao, Dandan Jia, Xiuying Cai, Chenchen Ye, Binhui Liu, Jiayu Wang, Jia |
Author_xml | – sequence: 1 givenname: Hangjun surname: Zhang fullname: Zhang, Hangjun – sequence: 2 givenname: Chenchen surname: Cai fullname: Cai, Chenchen – sequence: 3 givenname: Yingzhu surname: Wu fullname: Wu, Yingzhu – sequence: 4 givenname: Dandan surname: Shao fullname: Shao, Dandan – sequence: 5 givenname: Binhui surname: Ye fullname: Ye, Binhui – sequence: 6 givenname: Yue surname: Zhang fullname: Zhang, Yue – sequence: 7 givenname: Jiayu surname: Liu fullname: Liu, Jiayu – sequence: 8 givenname: Jia surname: Wang fullname: Wang, Jia – sequence: 9 givenname: Xiuying surname: Jia fullname: Jia, Xiuying email: hznujiaxiuying@126.com |
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Keywords | MC-LR Mitochondria Rana nigromaculata Endoplasmic reticulum Apoptosis Drinking water Deformation Toxicity Antioxidant In vitro Toxin Production Oxidation |
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Snippet | •MCLR can induce apoptosis on testes of Rana nigromaculata.•1μg/L MCLR (the drinking water standard level) has ecological risks on frogs.•MCLR induces frog... Previous studies have shown that toxins produced by toxic cyanobacterial blooms are hazardous materials. In the present study, 1 μg/L microcystin-LR (MC-LR)... |
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SubjectTerms | Animals Apoptosis Apoptosis - drug effects Applied sciences bcl-2-Associated X Protein - metabolism Caspases - metabolism Chemical engineering Cytochromes c - metabolism Drinking water and swimming-pool water. Desalination Endoplasmic Reticulum Exact sciences and technology Glutathione - metabolism Glutathione Peroxidase - metabolism Heat-Shock Proteins - metabolism Male Malondialdehyde - metabolism MC-LR Microcystins - toxicity Microscopy, Electron, Transmission Mitochondria Oxidative Stress Pollution Proto-Oncogene Proteins c-bcl-2 - metabolism Rana nigromaculata Ranidae Reactive Oxygen Species - metabolism Reactors Testis - drug effects Testis - metabolism Testis - ultrastructure Transcription Factor CHOP - metabolism Water Pollutants, Chemical - toxicity Water treatment and pollution |
Title | Mitochondrial and endoplasmic reticulum pathways involved in microcystin-LR-induced apoptosis of the testes of male frog (Rana nigromaculata) in vivo |
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