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

Abstract

Glucose‑regulated protein 75 (GRP75) is a member of the heat shock protein 70 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.

The Impairments of α-Synuclein and Mechanistic Target of Rapamycin in Rotenone-Induced SH-SY5Y Cells and Mice Model of Parkinson’s Disease

“…Expression of GRP75 was increased in SH-SY5Y cells by ROT treatment but decreased in midbrain and striatum of C57BL/6J mice. As previously reported, GRP75 overexpression in human DAergic cells enhanced vulnerability to ROT-induced cytotoxicity (Jin et al, 2006), but in vivo GRP75 overexpression reduced infarct size and protected against mitochondrial damage in a rat middle cerebral artery occlusion model of stroke (Xu et al, 2009) and a rat model of intracerebral hemorrhage (ICH) (Lv et al, 2017). GRP75 expression was also decreased in the mitochondrial fraction isolated from the SNpc of PD patients compared to controls (Jin et al, 2006).…”

Dietary Modifications of Nitrogen Intake Decreases Inflammation and Promotes Rejuvenation of Spleen in Aged Mice

“…In line with these data, it was recently shown that Grp75 over-expression inhibits inflammation and potentially inhibits neuronal apoptosis in a rat model of intracerebral haemorrhage [71]. In addition, Grp75 can inhibit reactive oxygen species accumulation, a mechanism that may be involved in the cytoprotective effect of Grp75 overexpression on glucose deprivation [72].…”

6-Hydroxydopamine Induces Neurodegeneration in Terminally Differentiated SH-SY5Y Neuroblastoma Cells via Enrichment of the Nucleosomal Degradation Pathway: a Global Proteomics Approach

“…The overexpression of HSPA9 was also reported to indirectly inhibit the stress-induced apoptosis by preventing the conformational change and translocation of Bax into mitochondria, indicating the suppression of apoptosis through Bax inactivation and inhibition of caspase activation (Stankiewicz et al 2005). A recent study has clarified that overexpression of HSPA9 prevents inflammation in a rat model of intracerebral haemorrhage through inhibition of inflammatory cytokines such as TNF-α, IL-β, Bax, and increased Bcl-2 levels (Lv et al 2017). Hence, we postulate that the overexpression of HSPE1 and HSPA9 in our study is closely connected to the cytoprotective mechanism of the neuronal cells to inhibit the avalanche of apoptotic mediators released in response to 6-OHDA treatment.…”