Exercise and menstrual cycle dependent expression of a truncated alternative splice variant of HIF1α in leukocytes

Abstract

HIF1 alpha is a subunit of the transcription factor HIF1 and a key regulator of angiogenesis, glucose metabolism and innate immune response. Recently, it has been shown that increases in free DNA in the plasma induce expression of HIF1 alpha. Large increases of free DNA in plasma are typically found after exercise. HIF1 alpha is therefore a potential candidate to orchestrate gene expression changes that initiate adaptations of the innate immune response after exercise. Although differential gene expression of HIF1 alpha in response to exercise has been studied extensively and increases in expression are described for the skeletal muscle, no significant changes have been reported in leukocytes so far. Here we show a highly significant increase in expression of the alternative splice variant HIF1 alpha-2 coding for a truncated 736 amino acid protein in peripheral blood derived mononuclear cells following a 1h aerobic exercise. In contrast, expression of the regular full length HIF1 alpha mRNA remained unchanged. Initial increase of HIF1 alpha-2 mRNA expression and subsequent return to baseline levels was not different between twelve men and nine women. The latter were studied in the follicular and luteal phases of their menstrual cycle. Baseline expression HIF1 alpha-2 but not HIF1 alpha-1 was significantly higher in the follicular phase than in the luteal phase. So far studies on the effects of HIF1 routinely measure only HIF1 alpha-1. Further studies are needed to elucidate the hitherto unknown influence of HIF1 alpha-2 on regulation of the innate immune response.