Research ReportCHMP4B, ESCRT-III associating protein, associated with neuronal apoptosis following intracerebral hemorrhage

- We imitate clinical ICH by injecting autologous blood into the basal ganglia of rat.
- We examine changes of CHMP4B level adjacent to the hematoma following ICH.
- Increasing expression of CHMP4B co-localized with neurons after ICH.
- Fas, FasL and active caspase-8 were paralleled with the variations of CHMP4B after ICH.
- Silencing of CHMP4B attenuate cellular death induced by hemin in vitro.

Charged multivesicular body protein (CHMP) represents a family of small helical proteins that contain an N-terminal basically charged region and a smaller C-terminal acidic region, which are highly conserved in all eukaryotes. CHMP4B, a core component of the endosomal sorting complex required for transport (ESCRT)-III, is requisite for endosomal sorting and other biological processes. Here, we demonstrate that CHMP4B may be involved in neuronal apoptosis in the processes of intracerebral hemorrhage (ICH). From the results of Western blot, immunohistochemistry and immunofluorescence, we obtained a significant up-regulation of CHMP4B in neurons adjacent to the hematoma following ICH. Increasing CHMP4B level was found to be accompanied by the up-regulation of Fas receptor (Fas), Fas ligand (FasL), active caspase-8, and active caspase-3. Besides, CHMP4B co-localized well with Fas and active caspase-3 in neurons, indicating its potential role in neuronal apoptosis. What׳s more, our in vitro study, using CHMP4B RNA interference in PC12 cells, further confirmed that CHMP4B might exert its pro-apoptotic function on neuronal apoptosis through extrinsic pathway. Thus, CHMP4B may play a role in promoting the brain damage following ICH.