Expression of Hypoxia-Inducible Factor-1α and Myoglobin in Rat Heart as Adaptive Response to Intermittent Hypobaric Hypoxia Exposure

Margaretha Herawati,Wardaya Wardaya,Wawan Mulyawan,Fanny Septiani Farhan,Frans Ferdinal,Sri Widia A Jusman,Mohamad Sadikin

doi:10.1016/j.hjb.2017.08.010

Abstract

The aim of this study was to investigate the influence of intermittent hypobaric hypoxia on the expression hypoxia adaptation proteins, namely hypoxia inducibla factor-1a (HIF-1a) and myoglobin (Mb). Twenty five male Sprague-Dawley rats were exposed to intermittent hypobaric hypoxia in a hypobaric chamber in Indonesian Air Force Institute of Aviation Medicine, for 49.5 minutes at various low pressure, 1 week interval for 4 times (day 1, 8, 15 and 22). HIF-1α and Mb protein were measured with ELISA. mRNA expression of Mb was measured with one step real time RT-PCR. HIF-1α protein levels increased after induction of hypobaric hypoxia and continues to decrease after induction of intermittent hypobaric hypoxia 3 times (ANOVA, p = 0.0437). mRNA expression and protein of Mb increased after induction of hypobaric hypoxia and continues to decrease after induction of intermittent hypobaric hypoxia 3 times (ANOVA, p = 0.0283; 0.0170), and both are strongly correlated (Pearson, r = 0.6307). The heart of rats adapted to intermittent hypoxia conditions by upregulation the expression of HIF-1a and myoglobin and then both return to normal level.

Highlights

Hypoxia is a condition in which oxygen supply cannot fulfill the need of an organism, its organ, or even a cell
About 2 decades ago, Semenza and Wang et al had found a protein factor which responded to hypoxia condition
Many biological processes are regulated by hypoxia-inducible factor (HIF)-1aelike erythropoiesis, angiogenesis, glucose metabolism, pH homeostasis, and blood pressure (Prijanti AR, 2010)

Summary

Introduction

Hypoxia is a condition in which oxygen supply cannot fulfill the need of an organism, its organ, or even a cell. In this situation, the subject (organism, organ, or cell) has to activate various mechanisms to maintain the energy level. The hypoxia condition induces adaptation responses to defend homeostasis in the body. Physiologic responses such as increased heart, pulse, and respiratory rates increase oxygen supply. Transcription factor hypoxia-inducible factor (HIF)-1a will be stabilized with HIF-1b. This heterodimer regulates many of the genes in hypoxic condition. High blood pressure was recorded during hypoxia, to increase oxygen distribution through red blood cells (Loscalzo J, 2010)

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