MitomiR-1736-3p regulates copper-induced mitochondrial pathway apoptosis by inhibiting AATF in chicken hepatocytes
Yuanxu Li1, Gaolong Zhong1, Lei Li1
1College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China.
Abstract:
Copper (Cu) is a toxic heavy metal pollutant. The hepatic toxicity of Cu has attracted widespread attention from researchers. However, its underlying mechanism remains elusive. Mitochondrial microRNAs (mitomiRs) are considered important factors in regulating mitochondrial and cellular functions, and their roles have been implicated in the mechanisms of metal toxicity. Therefore, this research revealed the changes in the mitomiRs expression profile of chicken liver after Cu exposure. It was ultimately determined that mitomiR-1736-3p can be involved in Cu-induced chicken liver damage by targeting AATF. In particular, our investigations have uncovered that exposure to Cu can trigger heightened levels of apoptosis in the hepatic tissue of chickens and primary chicken embryo hepatocytes (CEHs). It is noteworthy that we found upregulation of miR-1736-3p expression can exacerbate Cu-induced cell apoptosis, while inhibition of miR-1736-3p can effectively reduce apoptosis occurrence. Subsequently, we found that Cu-induced cell apoptosis could be restored by overexpressing AATF, while silencing AATF exacerbated the level of apoptosis. Fascinatingly, this change in apoptotic level is directly influenced by AATF on Bax and Bak1, rather than on p53 and Bcl-2. Overall, these findings suggest that the mitomiR-1736-3p/AATF axis mediates the mitochondrial pathway of cell apoptosis potentially involved in Cu-induced chicken liver toxicity.
Insights
Copper exposure causes liver damage in chickens by altering mitochondrial microRNAs (mitomiRs). Specifically, mitomiR-1736-3p targets AATF, influencing cell apoptosis and contributing to hepatic toxicity.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Cellular Biology
Background:
- Copper (Cu) is a significant heavy metal pollutant with known hepatic toxicity.
- The precise mechanisms underlying Cu-induced liver damage are not fully understood.
- Mitochondrial microRNAs (mitomiRs) play crucial roles in cellular functions and are implicated in metal toxicity.
Purpose of the Study:
- To investigate the impact of Cu exposure on the mitomiR expression profile in chicken liver.
- To elucidate the role of specific mitomiRs in Cu-induced hepatic toxicity.
- To identify the molecular targets and pathways involved in Cu toxicity.
Main Methods:
- Analysis of mitomiR expression profiles in chicken liver following Cu exposure.
- Investigation of the effects of mitomiR-1736-3p on apoptosis in chicken embryo hepatocytes (CEHs).
- Functional studies involving AATF overexpression and silencing to assess its role in Cu-induced apoptosis.
Main Results:
- Copper exposure altered the mitomiR expression profile in chicken liver.
- mitomiR-1736-3p was identified as a key player, targeting AATF and influencing apoptosis.
- Upregulation of mitomiR-1736-3p exacerbated Cu-induced apoptosis, while its inhibition reduced it.
- AATF modulated apoptosis by affecting Bax and Bak1 expression.
- The mitomiR-1736-3p/AATF axis was implicated in the mitochondrial pathway of apoptosis.
Conclusions:
- The mitomiR-1736-3p/AATF axis is a critical mediator in Cu-induced chicken liver toxicity.
- This axis influences the mitochondrial pathway of apoptosis, highlighting a novel mechanism of heavy metal-induced liver damage.
- Findings provide insights into the molecular basis of copper toxicity and potential therapeutic targets.
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