The Expression Changes of Vacuolar Protein Sorting 4B (VPS4B) Following Middle Cerebral Artery Occlusion (MCAO) in Adult Rats Brain Hippocampus

Abstract

Vacuolar protein sorting 4 (VPS4), is a member of ATPases associated with diverse cellular activities protein family. VPS4 is composed of VPS4A and VPS4B, VPS4B plays an important role in the lysosomal degradation pathway, intracellular protein trafficking, virus budding and abscission of cytokinesis. However, information regarding its distribution and possible function in the central nervous system is limited. Therefore, we performed a middle cerebral artery occlusion (MCAO) in adult rats and detected the dynamic changes of VPS4B in hippocampus CA1 subregion. We found that the VPS4B expression was increased strongly after MCAO and reached the peak after 3 days. VPS4B mainly located in the cytoplasm of neurons, but not astrocytes and microglia. Moreover, there was a concomitant up-regulation of active caspase-3. In vitro studies indicated that the up-regulation of VPS4B may be involved in oxygen-glucose deprivation-induced PC12 cell death. And knock-down of VPS4B in cultured differentiated PC12 cells by siRNA showed that VPS4B promoted the expression of active caspase-3. Collectively, all these results and MTT assay suggested that the up-regulation of VPS4B played an important role in the pathophysiology after MCAO, and further research is needed to have a good understanding of its function and mechanism.

A splicing mutation inVPS4Bcauses dentin dysplasia I

“…In addition, VPS4B has been shown to interact with the endosomal membrane to regulate the internalisation and lysosomal degradation of membrane proteins,30 and it also participates in intracellular protein trafficking, abscission of cytokinesis and virus budding 31. Depletion of VPS4B protein causes defects of nuclear morphology and chromosome segregation 19.…”

Vacuolar protein sorting 4B regulates apoptosis of intestinal epithelial cells via p38 MAPK in Crohn's disease

“…VPS4 may act as an important role in lysosomal targeting or extracellular secretion of αSYN which contribute to the intercellular propagation of Lewy pathology in Parkinson's disease (Hasegawa et al, 2011). Meanwhile, VPS4B was reported to be up-regulated and promoted neuronal cellular apoptosis through active caspase-3 after cerebral ischemia (Cui et al, 2014). However, the expression and possible contribution of VPS4B to apoptosis of IECs in CD has not been identified.…”

“…VPS4B may be a postulate tumor suppressor of breast cancer through promoting the degradation of EGFR (Lin et al, 2012). Some researchers reported, VPS4B can regulate the progression of non-small-cell lung cancer (NSCLC) (Liu et al, 2013), play a role in the Parkinson's disease (Hasegawa et al, 2011), and also participate in neuronal apoptosis after cerebral ischemia with a middle cerebral artery occlusion (MCAO) model (Cui et al, 2014). Without a doubt, VPS4B is a multifunctional protein, but its expression and potential functions in CD are not understood yet.…”

Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF

“…Expression of colec11 has been reported in neurons and is involved in innate immunity (Motomura et al, 2008 ; Ohtani et al, 2012 ). vpsb4 is known to interact with the pro-apoptotic pathway (Cui et al, 2014 ) and the autophagosome in neurodegenerative conditions (Han et al, 2012 ). The most strongly upregulated genes were related to response to stress and injury, such as activating transcription factor 3 (atf3) and small proline-rich repeat protein 1A (sprr1A).…”