Factors Affecting Hypoxia

INTRODUCTION

High altitude cause many problem in human being due to sudden fall in atmospheric pressure at higher altitude decreases the partial pressure of inspired oxygen and hence the driving pressure for gas exchange in the lungs [1]. For sustain a life aerobic organisms require oxygen is an essential element for their metabolic activity. It is used to final acceptor of electrons in the mitochondrial respiratory chain, where it allow the process of oxidative phosphorylation and the generation of cellular energy, in the form of adenosine triphosphate (ATP). Cell requires a constant ratio of ATP for the survival under the normoxic condition.[2,3] Therefore, hypoxia leads to a condition of which inadequate level of oxygen is supplied to the

HIF regulates the expression of many target genes in response to hypoxia. These genes include vascular endothelial growth factor, erythropoietin, and glycolytic enzymes that are transcriptionally induced under hypoxic conditions by HIF.[6,7] It is also known as oxygen-sensitive transcriptional activator (Qingdong et al., 2006) because it regulates the oxygen in human body. In human body HIF complex coordinates the myriad responses to decreased oxygen tension by promoting compensatory mechanisms acting at the cellular as well as organismal level that include enhancing the oxygen-carrying capacity of blood, decreasing cellular oxygen demand, and increasing glycolysis. HIFs are heterodimeric protein comprising of HIF-α subunits (i.e. HIF-1 α, HIF-2 α or HIF-3 α), and a constitutive HIF-1β subunit, it is also known as aryl hydrocarbon receptor nuclear translocator or ARNT, which together form the HIF-1, HIF-2 and HIF-3 transcriptional complexes, respectively [9]. The purpose of this review to provides the brief overview about HIF transcription factor, its regulation in normoxic condition and hypoxic condition and the current trend in HIF system how to inhibit the protein-protein interaction in HIF

EPO is a hormone which is required for the proliferation erythrocytes and undergoes hypoxia induced transcription (Semenza et al., 1991, Goldberg et al., 1988). HIF-1 complex is a master regulator of the transcription factor, which is comprises of two heterodimeric protein subunits i.e. α and β subunits (Wang et al., 1995). β subunit is identified as a binding partner of the aryl hydrocarbon receptor (Reyes et al., 1992) so it is also known as ARNT (the aryl hydrocarbon nuclear translocator). Both of the subunits of HIF-1 complex belong to the same family of proteins that contain basic helix-loop-helix (HLH) and PER-ARNT-SIM (PAS) motifs. These two motifs are important for the formation of heterodimerisation between the HIF-α and HIF-β subunits (Manolescu et al., 2009). Previous historyin HIF system tells that there are three HIF-α subunits are reported i.e. HIF-1α, HIF-2α or HIF-3α (Hogenesch et al., 1997). Out of the three α-subunits, HIF-1α and HIF-2α are the best studied. HIF-1α is ubiquitously expressed in human tissues, which has simple role in multiple physiological responses to hypoxia (Semenza, 1998). HIF-2α is expressed in endothelial cells such as lung, endothelium, and carotid body (Gordan et al., 2007). HIF-3α has similar to HIF-1α