PAQR3 protects against oxygen –glucose deprivation/reperfusion-induced injury through the ERK signaling pathway in N2A cells

AbstractCerebral ischemia –reperfusion injury is pivotal in the development of multiple-subcellular organelle and tissue injury after acute ischemic stroke. Recently, the Golgi apparatus (GA) has been shown to be a key subcellular organelle that plays an important role in neuroprotection against oxygen–glucose deprivatio n/reperfusion (OGD/R) injury. PAQR3, a scaffold protein exclusively localized in the GA, was originally discovered as a potential tumor suppressor protein. PAQR3 acts as a spatial regulator of Raf-1 that binds Raf-1 and sequesters it to the GA, where it negatively modulates the Ras/Raf/MEK/ERK signa ling pathway in tumor models. Studies suggest that suppression of the ERK pathway can alleviate OGD/R-induced cell apoptosis. However, whether PAQR3 has potential effects on ischemic stroke and the underlying mechanism(s) remain unexplored. The current study is the first to show that PAQR3 was signi ficantly downregulated in mouse neuroblastoma (N2A) cells upon OGD/R exposure, both at the mRNA and protein levels. Compared to that in controls, the mRNA level of PAQR3 began to decline at 0 h (0 h) after reperfusion, while the protein level began to decline at 4 h. Furthermore, overexpression o f PAQR3 reduced OGD/R-induced apoptosis. The mRNA and protein levels of total ERK1 and ERK2 were unaltered, while activated p-ERK1 and p-ERK2 were decreased in N2A cells transfected with a PAQR3 expression vector after OGD for 4 h plus 24 h of reperfusion. Collectivel...
Source: Journal of Molecular Histology - Category: Laboratory Medicine Source Type: research