Induction of apoptosis in the gonads of Mytilus edulis by metformin and increased temperature, via regulation of HSP70, CASP8, BCL2 and FAS

Wulan Koagouw; Richard J. Hazell; Corina Ciocan

doi:10.1016/j.marpolbul.2021.113011

Induction of apoptosis in the gonads of Mytilus edulis by metformin and increased temperature, via regulation of HSP70, CASP8, BCL2 and FAS

Wulan Koagouw, Richard J. Hazell, Corina Ciocan

Research output: Contribution to journal › Article › peer-review

Abstract

Pharmaceutically active compounds have been considered contaminants of emerging concern, in response to evidence that these substances may adversely affect aquatic organisms. Here we expose mussels for 7 days to metformin, the most commonly prescribed anti-diabetes treatment, at a concentration of 40 μg/L and a high temperature of 20 °C. The apoptosis-related genes HSP70, CASP8, BCL2 and FAS showed variation in expression in gonadal tissue. The results suggest that complex interactions between these genes are modulating the onset of apoptotic changes such as atresia and follicle degeneration. The temperature induced apoptosis may be initiated by overexpression of CASP8. Conversely, metformin may induce apoptosis by suppressing the anti-apoptotic gene BCL2, thus promoting the process. Interestingly, apoptosis and follicle degeneration are likely FAS-mediated, following the synergistic effect of metformin and temperature. The potential of metformin to act as a non-traditional EDC, due to its impact on the reproductive system in mussels is discussed.

Original language	English
Article number	113011
Journal	Marine Pollution Bulletin
Volume	173
Issue number	Pt A
DOIs	https://doi.org/10.1016/j.marpolbul.2021.113011
Publication status	Published - 9 Oct 2021

Bibliographical note

Funding Information:
The authors would like to thank Dr. Darren McCabe and Lisa Jolliffe for their laboratory assistance. This research is funded by the Ministry of Research, Technology, and Higher Education (MRTHE) Republic of Indonesia through Research and Innovation in Science and Technology Project (RISET-Pro).

Funding Information:
This work was supported by Ministry of Research, Technology, and Higher Education (MRTHE) Republic of Indonesia through Research and Innovation in Science and Technology Project (RISET-Pro). The funding body has no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Keywords

Apoptosis
Metformin
mRNA expression
Multiple stressors
Mussels
Temperature

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10.1016/j.marpolbul.2021.113011

MPB_D_21_00567_R2Accepted author manuscript, 1.1 MBLicence: CC BY-NC-ND

Cite this

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title = "Induction of apoptosis in the gonads of Mytilus edulis by metformin and increased temperature, via regulation of HSP70, CASP8, BCL2 and FAS",

abstract = "Pharmaceutically active compounds have been considered contaminants of emerging concern, in response to evidence that these substances may adversely affect aquatic organisms. Here we expose mussels for 7 days to metformin, the most commonly prescribed anti-diabetes treatment, at a concentration of 40 μg/L and a high temperature of 20 °C. The apoptosis-related genes HSP70, CASP8, BCL2 and FAS showed variation in expression in gonadal tissue. The results suggest that complex interactions between these genes are modulating the onset of apoptotic changes such as atresia and follicle degeneration. The temperature induced apoptosis may be initiated by overexpression of CASP8. Conversely, metformin may induce apoptosis by suppressing the anti-apoptotic gene BCL2, thus promoting the process. Interestingly, apoptosis and follicle degeneration are likely FAS-mediated, following the synergistic effect of metformin and temperature. The potential of metformin to act as a non-traditional EDC, due to its impact on the reproductive system in mussels is discussed.",

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author = "Wulan Koagouw and Hazell, {Richard J.} and Corina Ciocan",

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AU - Ciocan, Corina

N1 - Funding Information: The authors would like to thank Dr. Darren McCabe and Lisa Jolliffe for their laboratory assistance. This research is funded by the Ministry of Research, Technology, and Higher Education (MRTHE) Republic of Indonesia through Research and Innovation in Science and Technology Project (RISET-Pro). Funding Information: This work was supported by Ministry of Research, Technology, and Higher Education (MRTHE) Republic of Indonesia through Research and Innovation in Science and Technology Project (RISET-Pro). The funding body has no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

PY - 2021/10/9

Y1 - 2021/10/9

N2 - Pharmaceutically active compounds have been considered contaminants of emerging concern, in response to evidence that these substances may adversely affect aquatic organisms. Here we expose mussels for 7 days to metformin, the most commonly prescribed anti-diabetes treatment, at a concentration of 40 μg/L and a high temperature of 20 °C. The apoptosis-related genes HSP70, CASP8, BCL2 and FAS showed variation in expression in gonadal tissue. The results suggest that complex interactions between these genes are modulating the onset of apoptotic changes such as atresia and follicle degeneration. The temperature induced apoptosis may be initiated by overexpression of CASP8. Conversely, metformin may induce apoptosis by suppressing the anti-apoptotic gene BCL2, thus promoting the process. Interestingly, apoptosis and follicle degeneration are likely FAS-mediated, following the synergistic effect of metformin and temperature. The potential of metformin to act as a non-traditional EDC, due to its impact on the reproductive system in mussels is discussed.

AB - Pharmaceutically active compounds have been considered contaminants of emerging concern, in response to evidence that these substances may adversely affect aquatic organisms. Here we expose mussels for 7 days to metformin, the most commonly prescribed anti-diabetes treatment, at a concentration of 40 μg/L and a high temperature of 20 °C. The apoptosis-related genes HSP70, CASP8, BCL2 and FAS showed variation in expression in gonadal tissue. The results suggest that complex interactions between these genes are modulating the onset of apoptotic changes such as atresia and follicle degeneration. The temperature induced apoptosis may be initiated by overexpression of CASP8. Conversely, metformin may induce apoptosis by suppressing the anti-apoptotic gene BCL2, thus promoting the process. Interestingly, apoptosis and follicle degeneration are likely FAS-mediated, following the synergistic effect of metformin and temperature. The potential of metformin to act as a non-traditional EDC, due to its impact on the reproductive system in mussels is discussed.

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Induction of apoptosis in the gonads of Mytilus edulis by metformin and increased temperature, via regulation of HSP70, CASP8, BCL2 and FAS

Abstract

Bibliographical note

Keywords

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