Sublethal effects of dimethoate on energy metabolism and its link to cellular senescence due to impaired mitochondrial respiration and ATP production in SH-SY5Y cells
3
Issued Date
2025-09-01
Resource Type
ISSN
00483575
eISSN
10959939
Scopus ID
2-s2.0-105008657226
Journal Title
Pesticide Biochemistry and Physiology
Volume
213
Rights Holder(s)
SCOPUS
Bibliographic Citation
Pesticide Biochemistry and Physiology Vol.213 (2025)
Suggested Citation
Pearngam P., Promthep K., Prasertporn T., Songsomboon K., Polvat T., Charoenkul J., Mukda S., Govitrapong P., Nopparat C., Panmanee J. Sublethal effects of dimethoate on energy metabolism and its link to cellular senescence due to impaired mitochondrial respiration and ATP production in SH-SY5Y cells. Pesticide Biochemistry and Physiology Vol.213 (2025). doi:10.1016/j.pestbp.2025.106520 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110947
Title
Sublethal effects of dimethoate on energy metabolism and its link to cellular senescence due to impaired mitochondrial respiration and ATP production in SH-SY5Y cells
Corresponding Author(s)
Other Contributor(s)
Abstract
Abstract Dimethoate (DM), a widely used organophosphate pesticide, induces significant alterations in mitochondrial-related proteomes of SH-SY5Y cells without directly affecting cell viability. After, cells were exposed to 100 μM DM for 48 h, proteomic analysis revealed that 27 proteins associated with cellular metabolism and mitochondrial function were notably altered, affecting pathways such as oxidative phosphorylation, electron transport chain, and ATP synthesis. At sublethal concentrations, DM reduced mitochondrial ATP production, oxygen consumption rates (OCR), basal and maximal respiration, while preserving spare respiratory capacity (SRC) and proton leak, indicating maintained mitochondrial membrane integrity. Despite this, DM exposure caused mitochondrial membrane depolarization and increased mitochondrial superoxide production. These mitochondrial alterations were accompanied by enhanced cellular senescence, marked by p53-independent p21 activation, p38 MAPK activation, increased senescence-associated β-galactosidase (SA-β-gal) activity, and disrupted cell cycle progression. Additionally, DM treatment led to upregulation of DNA damage response (DDR) proteins and downregulation of proteins involved in DNA repair and genome stability. Although early-stage apoptosis was observed, elevated Bcl-2 expression suggested a shift toward apoptosis resistance and senescence. DM also disrupted energy-sensing pathways by increasing AMPK subunit expression, yet suppressed autophagy, as indicated by decreased p-mTOR, p-Beclin-1, and LC3-II/I ratios. Collectively, these findings highlight a complex interplay between mitochondrial dysfunction, cellular senescence, and survival mechanisms, suggesting potential long-term effects of DM exposure on cellular health and aging processes.