Overexpression of GRP75 inhibits inflammation in a rat model of intracerebral hemorrhage.

Abstract

Glucose‑regulated protein75 (GRP75) is a member of the heat shock protein70 family and previous studies have demonstrated that GRP75 is involved in diseases of the central nervous system. However, the biological function of GRP75 in intracerebral hemorrhage (ICH) remains to be clarified. Thus, the aim of the present study was to evaluate the effects of GRP75 in a rat model of ICH. Western blotting was used to detect the protein expression of GRP75, active caspase‑3, Bax, Bcl‑2, p‑Akt and Akt in brain tissues following ICH. The levels of tumor necrosis factor‑α (TNF‑α) and interleukin (IL)‑1β were evaluated using ELISA assay. Expression of GRP75 mRNA and protein was demonstrated to be reduced in the brain tissues of rats with ICH compared with sham‑operated rats. In addition, overexpression of GRP75 in brain tissues with ICH significantly inhibited the production of the inflammatory cytokines TNF‑α and IL-1β and increased Bcl‑2/decreased Bax levels compared with ICH alone. Furthermore, overexpression of GRP75 in brain tissues with ICH resulted in significantly increased phosphorylation of Akt compared with ICH alone. Therefore, the present study demonstrated, for the first time to the best of our knowledge, significantly reduced GRP75 expression in brain tissues following ICH, and that overexpression of GRP75 inhibits inflammation and potentially inhibits neuronal apoptosis in a rat model of ICH. GRP75 may, therefore, represent a promising target in the treatment of ICH.