Molecular Signalling Network and Response Mechanism Associated with Hypoxia in High Altitude Mammals

: World highest and largest altitude to be called is Qinghai-Tibetan plateau (QTB), which harbors unique animal and plant species. Mammals that inhabit the higher altitude regions have adapted well to the hypoxic conditions. One of Main stressor at high altitude is Hypoxia. Metabolic responses to hypoxia play important roles in cell survival strategies and disease However, the homeostatic alterations that equilibrate variations in demand and supply of energy to maintain organismal function in prolonged low O2 circumstances persist partly understood, making it problematic to differentiate adaptive from maladaptive responses in hypoxia. Tibetans and yaks are two perfect examples innate to the plateau for high altitude adaptation. By the scan of whole genome EPAS1 and EGLN1 identified as key genes associated in sustain haemoglobin concentration in high altitude mammals for adaptation. The yak is much ancient mammal existed on QTB than human, it is therefore possible that natural selection had represented on a diverse group of genes/pathways in yaks. Physiological characters are extremely informative in revealing molecular networks associated in inherited adaptation, in addition to whole-genome adaptive changes at the DNA sequence level. Gene expression can be changed by a variety of signals originating from the environment, and hypoxia is the main factor amongst them. The hypoxia-inducible factors (HIF-1α and EPAS1/HIF-2α) are the main oxygen homeostasis that role as maestro regulators of adaption in hypoxic reaction to molecular mechanisms. Basis of this review is to present recent information of molecular mechanism that involved in hypoxia that regulates candidate genes and proteins. Many transcriptional responses toward hypoxia are facilitated via HIFs that switch the number of gene expressions and helps to angiogenesis, erythropoiesis, metabolic reprogramming and metastasis. HIFs also activate a number of signal points toward a solid association between hypoxia, the misfolded proteins accumulation in the endoplasmic reticulum in stress and unfolded protein response (UPR) activation. It was observed that in high-altitude pregnancy have low birth weight ∼100 g per1000 m of climb. It may involve variation in events of energy demanding, like protein synthesis. Prolonged hypobaric hypoxia causes placental ER stress, which, in turn, moderates protein synthesis and reduces proliferation. Further, Cardiac hypertrophy by cytosolic Ca2+ raise and Ca2+/calmodulin, calcineurin stimulation, NF-AT3 pathway might be caused by imbalance in Sarcoplasmic reticulum ER Ca2, might be adaptive in beginning but severe later.