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Mitochondrial ROS-mediated ribosome stalling and GCN2 activation are partially involved in 1-nitropyrene-induced steroidogenic inhibition in testes.
- Source :
-
Environment International . Sep2022, Vol. 167, pN.PAG-N.PAG. 1p. - Publication Year :
- 2022
-
Abstract
- In the past 50 years, testosterone (T) level in men has declined gradually. In this research, we discovered that acute exposure to 1-nitropyrene (1-NP), an environmental stressor from polluted atmosphere, reduced T contents by downregulating steroidogenic proteins in mouse testes and Leydig cells. Acute 1-NP exposure caused GCN2 activation and eIF2α phosphorylation, a marker of integrated stress, in mouse testes and Leydig cells. GCN2iB, a selective GCN2 kinase inhibitor, and siGCN2, the GCN2-targeted short interfering RNA, attenuated 1-NP-induced reduction of steroidogenic proteins in Leydig cells. Mechanistically, mitochondrial membrane potential was reduced and ATP5A, UQCRC2, SDHB and NDUFB8, four OXPHOS subunits, were reduced in 1-NP-exposed Leydig cells. Cellular mitochondrial respiration was inhibited and ATP production was reduced. Moreover, mitochondrial reactive oxygen species (ROS) were elevated in 1-NP-exposed Leydig cells. The interaction between GCN2 and uL10, a marker of ribosome stalling, was observed in 1-NP-exposed Leydig cells. MitoQ, a mitochondria-targeted antioxidant, attenuated1-NP-evoked ATP depletion and ribosome stalling in Leydig cells. Moreover, MitoQ suppressed 1-NP-caused GCN2 activation and eIF2α phosphorylation in Leydig cells. In addition, MitoQ alleviated 1-NP-induced steroidogenic inhibition in mouse testes. In conclusion, mitochondrial ROS-mediated ribosome stalling and GCN2 activation are partially involved in environmental stress-induced steroidogenic inhibition in testes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01604120
- Volume :
- 167
- Database :
- Academic Search Index
- Journal :
- Environment International
- Publication Type :
- Academic Journal
- Accession number :
- 158482212
- Full Text :
- https://doi.org/10.1016/j.envint.2022.107393