HIF-1α Involves in Neuronal Apoptosis after Traumatic Brain Injury in Adult Rats

Abstract

Hypoxia-inducible factor-1α (HIF-1α), a well-identified hypoxia-related protein, is involved in regulating the biological functions of various cell types including neurons. The traditional biological function of HIF-1α is promoting the transcription of some pro-survival genes when exposing to low oxygen conditions. Meanwhile, some studies also point out that HIF-1α shows the detrimental role in several central nervous system (CNS) disorders. Up to now, the knowledge of HIF-1α function in CNS is still limited. To investigate whether HIF-1α is involved in CNS impairment and repair, we employed a traumatic brain injury model in adult rats. Upregulation of HIF-1α was observed in the injured brain cortex by western blot analysis and immunohistochemistry staining. Terminal deoxynucleotidyl transferase deoxy-UTP nick-end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining suggested that HIF-1α was relevant to neuronal apoptosis after brain injury. In addition, glutamate excitotoxic model of primary cortex neurons was introduced to further investigate the role of HIF-1α in neuronal apoptosis; the result implied HIF-1α was associated with the regulation of p53 and BNIP3 in the apoptotic neurons. Based on our data, we suggested that HIF-1α might play an important role in neuronal apoptosis after traumatic brain injury in rat, which might also provide a basis for the further study on its role in regulating the transcription of target genes in apoptotic neurons, and might gain a novel strategy for the clinical therapy for traumatic brain injury.

Repeated Administration of Ketamine can Induce Hippocampal Neurodegeneration and Long-Term Cognitive Impairment via the ROS/HIF-1a Pathway in Developing Rats

“…L-carnitine is an antioxidant that can control the excessive production of ROS and that was shown to protect against neuronal apoptosis [10]. Based on evidence that excessive ROS could activate HIF-1α and that severe HIF-1α activation could induce neuronal apoptosis [21,43,44,45,49,53], our finding suggests that ketamine-induced neurodegeneration was mediated by the upregulation of ROS, which in turn caused upregulation of HIF-1α. When excessive generation of ROS in ketamine-exposed hippocampal neurons was neutralized by L-carnitine, HIF-1α activity, and therefore the percentage of apoptotic neurons, was comparable to control levels.…”

Distinguishing the Unique Neuropathological Profile of Blast Polytrauma

“…HIF-1 α is a transcription factor that is involved in several injury modalities where hypoxia occurs, including TBI [51]. Even though HIF-1 α has been shown to play a role in TBI progression and cerebral ischemia, few studies have examined its role after mTBI and it has not been investigated in relation to BPT [52, 53].…”

Overexpression of FABP3 inhibits human bone marrow derived mesenchymal stem cell proliferation but enhances their survival in hypoxia

“…TP53 encodes the tumor suppressor protein containing transcriptional activation. The encoded protein responds to diverse cellular stresses to down-regulate expression of PCNA and up-regulate expression of BCL2, CASP3 and SERTAD1, thereby inducing cell cycle arrest, and enhances programmed cell death or changes in metabolism [35–38]. In contradistinction, genes promoting mitosis, nuclear division and DNA synthesis were down regulated, such as CDK1, CDC6, CCNB1, CCNB2, MCM and APC.…”