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 inJournal of hazardous materials Vol. 252-253; pp. 382 - 389
Main Authors Zhang, Hangjun, Cai, Chenchen, Wu, Yingzhu, Shao, Dandan, Ye, Binhui, Zhang, Yue, Liu, Jiayu, Wang, Jia, Jia, Xiuying
Format Journal Article
LanguageEnglish
Published Kidlington 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.
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&lt;0.01) and inhibiting the protein expression of Bcl-2 with prolonged exposure (p&lt;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
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Keywords MC-LR
Mitochondria
Rana nigromaculata
Endoplasmic reticulum
Apoptosis
Drinking water
Deformation
Toxicity
Antioxidant
In vitro
Toxin
Production
Oxidation
Language English
License CC BY 4.0
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SSID ssj0001754
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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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StartPage 382
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
URI https://dx.doi.org/10.1016/j.jhazmat.2013.03.017
https://www.ncbi.nlm.nih.gov/pubmed/23548922
https://search.proquest.com/docview/1353479173
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