Abstract
BackgroundThe effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues.MethodsForty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α).ResultsIncreased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α.ConclusionsAcute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.
Highlights
The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear
Telomere shortening is a well-established cause of cellular senescence and apoptosis that can be induced by many intrinsic and extrinsic factors, and telomere length is positively related to the life span of cells
The results showed that compared with control group, the telomere length was significantly longer in rats exposed to severe hypoxia for 1–7 days (p < 0.05)
Summary
The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. It has been well documented that acute exposure to hypoxia at high altitude will cause serious damage to a wide variety of human organs, in particular the heart and lung tissues. It is known that acute exposure to severe hypoxia at high altitude could induce adaptive response of cells to hypoxia, and damage such as cellular senescence and apoptosis can occur when cells no longer have to ability to withstand hypoxia. Telomere shortening is a well-established cause of cellular senescence and apoptosis that can be induced by many intrinsic and extrinsic factors, and telomere length is positively related to the life span of cells.
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