Hypoxia inducible factor-1: its potential role in cerebral ischemia

Abstract

A divergence in the supply and consumption of oxygen in brain tissue initiates complex cycle of biochemical and molecular events resulting in neuronal death. To overcome such adverse situation, the tissue has to adopt some cellular mechanisms such as induction of various transcription factors, such as hypoxia inducible factor (HIF). It is a transcriptional regulator of oxygen homeostasis and key factor to generate the adaptive responses through upregulation of various target genes involved in the erythropoiesis, angiogenesis as well as glucose metabolism and transport. On the other hand, some studies do suggest that HIF also plays a detrimental role in ischemic reperfusion (I/R) injury by inducing the pro apoptotic molecules, cytokines such as Nix, BNip3 and IL-20 which cause mitochondrial dysfunction leading to cell death. Hence, modulation of HIF-1 activity seems to provide an innovative therapeutic target to reduce the cellular damage, which arises from ischemic injury. Apart from traditional oxygen dependent HIF regulation, the focus has now shifted towards oxygen independent regulation in cell specific manner through reactive oxygen species (ROS) involving hypoxia associated factor (HAF), and HSP90 etc. Therefore, future development of such small molecule regulators for HIF-1 stability and signaling may prove useful to therapeutically target for enhancing recovery and repair in I/R injury.