TY - JOUR

T1 - The Effects of Severe Hypobaric Hypoxia and Inhibition of Hypoxia-Inducible Factor-1 (HIF-1) on Biomarkers of Cardiac and Skeletal Muscle Injury in Rats

AU - Fedorov, D. A.

AU - Frolova, M. Yu.

AU - Krasovskaya, I. E.

AU - Kuleva, N. V.

N1 - Fedorov, D.A., Frolova, M.Y., Krasovskaya, I.E. et al. The Effects of Severe Hypobaric Hypoxia and Inhibition of Hypoxia-Inducible Factor-1 (HIF-1) on Biomarkers of Cardiac and Skeletal Muscle Injury in Rats. BIOPHYSICS 64, 808–811 (2019) doi:10.1134/S000635091905004X

PY - 2019

Y1 - 2019

N2 - The goal of the present study was to investigate the molecular mechanisms that underlie heart and skeletal muscle damage in male Wistar rats weighing 200–250 g in response to a 3-h exposure to 180 mm Hg (5% O2) in the model of severe hypobaric hypoxia. It has been demonstrated that the level of the cardiac biomarker troponin I in the blood plasma of rats exposed to severe hypobaric hypoxia for 3 h increased significantly compared to the control group, indicating myocardial injury. At the same time, the administration of the HIF-1α transcription factor inhibitor did not affect the plasma level of troponin I. In contrast, the release of the non-specific biomarker myoglobin into the bloodstream did not increase in response to hypoxia compared to the control animals. In addition, 24 h after the exposure to severe hypobaric hypoxia the serum myoglobin level was significantly lower in animals administered with the HIF-1α inhibitor topotecan than in rats that did not receive topotecan. Therefore, it may be assumed that the inhibition of the HIF-1α transcription factor 10 min before exposure to severe hypobaric hypoxia reduces skeletal muscle damage. The mechanisms that affect the adaptation of heart and skeletal muscles to hypoxia are discussed.

AB - The goal of the present study was to investigate the molecular mechanisms that underlie heart and skeletal muscle damage in male Wistar rats weighing 200–250 g in response to a 3-h exposure to 180 mm Hg (5% O2) in the model of severe hypobaric hypoxia. It has been demonstrated that the level of the cardiac biomarker troponin I in the blood plasma of rats exposed to severe hypobaric hypoxia for 3 h increased significantly compared to the control group, indicating myocardial injury. At the same time, the administration of the HIF-1α transcription factor inhibitor did not affect the plasma level of troponin I. In contrast, the release of the non-specific biomarker myoglobin into the bloodstream did not increase in response to hypoxia compared to the control animals. In addition, 24 h after the exposure to severe hypobaric hypoxia the serum myoglobin level was significantly lower in animals administered with the HIF-1α inhibitor topotecan than in rats that did not receive topotecan. Therefore, it may be assumed that the inhibition of the HIF-1α transcription factor 10 min before exposure to severe hypobaric hypoxia reduces skeletal muscle damage. The mechanisms that affect the adaptation of heart and skeletal muscles to hypoxia are discussed.

KW - hypoxia, myoglobin, troponin I, topotecan,hypoxia-inducible factor 1-alpha (HIF-1α), myocardium

KW - myoglobin

UR - http://link.springer.com/article/10.1134/S000635091905004X

M3 - Article

VL - 64

SP - 808

EP - 811

JO - Biophysics (Russian Federation)

JF - Biophysics (Russian Federation)

SN - 0006-3509

IS - 5

ER -