Abstract
Prohibitin2 (PHB2) is a ubiquitous, evolutionarily strongly conserved protein. It is one of the components of the prohibitin complex, which comprises two highly homologous subunits, PHB1 and PHB2. PHB2 is present in various cellular compartments including the nucleus and mitochondria. Recent studies have identified PHB2 as a multifunctional protein that controls cell proliferation, apoptosis, cristae morphogenesis and the functional integrity of mitochondria. However its distribution and function in the central nervous system (CNS) are not well understood. In this study, we examined PHB2 expression and cellular localization in rats after acute traumatic brain injury (TBI). Western Blot analysis showed PHB2 level was significantly enhanced at five days after injury compared to control, and then declined during the following days. The protein expression of PHB2 was further analyzed by immunohistochemistry. In comparison to contralateral cerebral cortex, we observed a highly significant accumulation of PHB2 at the ipsilateral brain. Immunofluorescence double-labeling showed that PHB2 was co-expressed with NeuN, GFAP. Besides, PHB2 also colocalized with activated caspase-3 and PCNA. To further investigate the function of PHB2, primary cultured astrocytes and the neuronal cell line PC12 were employed to establish a proliferation model and an apoptosis model, respectively, to simulate the cell activity after TBI to a certain degree. Knocking down PHB2 by siRNA partly increased the apoptosis level of PC12 stimulated by H2O2. While the PHB2 was interrupted by siRNA, the proliferation level of primary cultured astrocytes was inhibited notably than that in the control group. Together with our data, we hypothesized that PHB2 might play an important role in CNS pathophysiology after TBI.
Highlights
Traumatic brain injury (TBI) is a most serious cause of injury related hospitalization, disability, and death throughout the world which can cause a significant loss of productive years and the necessity for long term care placing a large economic burden on society [1,2,3,4]
TBI is composed of a primary insult resulting from the direct result of the mechanical effects of impact and inertial forces, and a secondary insult which can induce a progressive cascade of related events in the brain damage and death of the TBI suffer that contribute to neuronal cell death, astrocyte proliferation, and microglia activation, including ischemia, brain edema, diffuse axonal injury, excitotoxicity, radical-mediated damage, and mitochondrial dysfunction [6,7,8,9,10,11,12]
Western Blot assays were performed to confirm the temporal pattern of PHB2 expression during traumatic brain injury (TBI)
Summary
Traumatic brain injury (TBI) is a most serious cause of injury related hospitalization, disability, and death throughout the world which can cause a significant loss of productive years and the necessity for long term care placing a large economic burden on society [1,2,3,4]. The prognosis for TBI patients remains poor due to the development of cerebral edema, elevated intracranial pressure, neuronal and vascular injury, and long-term cognitive dysfunction. Prohibitin (PHB2) is ubiquitous, evolutionarily conserved proteins that is present in multiple cellular compartments. PHB1 is a potential tumor suppressor protein, which has been shown to inhibit cell proliferation and repress E2F transcriptional activity [21,22]. PHB2 acts as a transcriptional repressor for MAF2 and MyoD [27,28,29] It has been reported by Hideaki and Sachihiro, that interfering in the expression of PHB2 in Hela cells can resulted in premature sister-chromatid separation and defects in chromosome congression accompanied by mitotic arrest by spindle-checkpoint activation [30]. PHB2 can interact with HAX-1 to inhibit apoptosis and regulate the mitochondrial morphology [31,32,33]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
