Scorpion venom heat-resistant peptide alleviates mitochondrial dynamics imbalance induced by PM2.5 exposure by downregulating the PGC-1α/SIRT3 signaling pathway.

Abstract

Background: Epidemiological inquiry reveals that neuroinflammation and mitochondrial dysfunction caused by PM_2.5 exposure are associated with Alzheimer's disease. Nevertheless, the molecular mechanisms of mitochondrial dynamics and neuroinflammation induced by PM_2.5 exposure remain elusive. In this study, our objective was to explore the impact of PM_2.5 on mitochondrial dynamics and neuroinflammation, while also examining the reparative potential of scorpion venom heat-resistant synthetic peptide (SVHRSP).

Methods: Western blot and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were employed to ascertain the protein and gene levels of IL-1β, IL-6, and TNF-α in BV2 cells. The concentration of IL-6 in the supernatant of the BV2 cell culture was measured by enzyme-linked immunosorbent assay. For the assessment of mitochondrial homeostasis, western blot, RT-qPCR, and cellular immunohistochemistry methods were utilized to investigate the protein and gene levels of DRP1 and MFN-2 in HT22 cells. In the context of signal pathway analyses, western blot, RT-qPCR, and immunofluorescence techniques were employed to detect the protein and gene expressions of PGC-1α and SIRT3 in HT22 cells, respectively. Following the transfection with siPGC-1αRNA, downstream proteins of PGC-1α/SIRT3 pathway in HT22 cells were investigated by Western blot and RT-qPCR.

Results: The experimental findings demonstrated that exposure to PM_2.5 exacerbated neuroinflammation, resulting in elevated levels of IL-1β, IL-6, and TNF-α. Furthermore, it perturbed mitochondrial dynamics, as evidenced by increased DRP1 expression and decreased MFN-2 expression. Additionally, dysfunction was observed in the PGC-1α/SIRT3 signal pathway. However, intervention with SVHRSP ameliorated the cellular damage induced by PM_2.5 exposure.

Conclusions: SVHRSP alleviated neuroinflammation and mitochondrial dynamics imbalance induced by PM_2.5 exposure by downregulating the PGC-1α/SIRT3 signaling pathway.