S100A1 expression is increased in spinal cord injury and promotes inflammation, oxidative stress and apoptosis of PC12 cells induced by LPS via ERK signaling.

Abstract

Spinal cord injury (SCI) is a severe neurological disorder and the molecular mechanisms leading to its poor prognosis remain to be elucidated. S100A1, a mediator of Ca2+ handling of sarcoplasmic reticulum and mitochondrial function, operates as an endogenous danger signal (alarmin) associated with inflammatory response and tissue injury. The aim of the present study was to investigate the expression and biological effects of S100A1 in SCI. A rat model of SCI and a PC12 cell model of lipopolysaccharide (LPS)‑induced inflammation were established to examine S100A1 expression at the mRNA and protein levels. The inflammation level, which was mediated by S100A1, was determined based on inflammatory factor (IL‑1β, IL‑6 and TNF‑α) and anti‑inflammatory factor (IL‑10) expression. The effects of S100A1 on cellular oxidation and anti‑oxidation levels were observed by detecting the levels of reactive oxygen species, superoxide dismutase, catalase activities and nuclear factor erythroid 2‑related factor 2 expression. The protein levels of Bax, Bcl2 and cleaved caspase‑3 were used for the evaluation of the effects of S100A1 on apoptosis. Phosphorylated (p‑)ERK1/2 expression was used to evaluate the effects of S100A1 on ERK signaling. The results revealed that S100A1 expression was significantly upregulated invivo and invitro in the PC12 cell model of LPS‑inflammation. The silencing and overexpression of S100A1 helped alleviate and aggravate LPS‑induced inflammation, oxidative stress and apoptosis levels, respectively. S100A1 was found to regulate the ERK signaling pathway positively. An inhibitor of ERK signaling (MK‑8353) partially abolished the promoting effects of the overexpression of S100A1 on inflammation, oxidative stress damage and apoptosis. In conclusion, S100A1 expression was elevated in model of SCI and in the PC12 cell model of LPS‑induced inflammation. Furthermore, the overexpression/silencing S100A1 aggravated/mitigated the inflammation, oxidative stress damage and the apoptosis of LPS‑stimulated PC12 cells via the ERK signaling pathway. The present study revealed the mechanism of S100A1 in SCI, which provided a new theoretic reference for future research on SCI.