Organ-specificity of HIF-1 alpha level and DNA fragmentation in rats exposed to chronic hypoxia

Although hypoxia-inducible factor-1a (HIF-1a) is the main transducer of hypoxia, its capacity to accumulate in vivo during chronic hypoxia is yet to be addressed. HIF-1a persistence in hypoxic tissues is relevant when different organs are exposed to the same decrease in arterial blood PO2. We test the hypothes is that hypoxemia causes different HIF-1a responses in various organs. To assess how HIF-1a affects downstream genes regulation, we selected apoptosis as a phenotype linked to cell viability. We measured HIF-1a (immunoperoxidase staining, quantitative immunofluorescence(TUNEL) in heart, liver, kidney, gastrocnemius and brain of rats exposed to 10 or 21% O2 for 2 weeks. HIF-1a accumulation in hypoxic tissues has the capacity to become a sustained phenomenon during hypoxia, but each organ responded differently, despite the same arterial PO2. While marked in brain, muscle and kidney cortex, HIF-1a increase was undetectable in heart and liver. In kidney medulla, HIF-1a was high in both normoxia and hypoxia. By contrast, the apoptotic response to hypoxia was marked in heart, slight in kidney medulla and undetectable in the other organs, indicating that the apoptotic pathway may be triggered by HIF-1a-independent mechanisms. These data emphasize that the array of responses elicited by inadequate O2 supply with respect to needs is very specific for each tissue and cell. and western blot) and DNA fragmentation (TUNEL) in heart, liver, kidney, gastrocnemius and brain of rats exposed to 10 or 21% O2 for 2 weeks. HIF-1a accumulation in hypoxic tissues has the capacity to become a sustained phenomenon during hypoxia, but each organ responded differently, despite the same arterial PO2. While marked in brain, muscle and kidney cortex, HIF-1a increase was undetectable in heart and liver. In kidney medulla, HIF-1a was high in both normoxia and hypoxia. By contrast, the apoptotic response to hypoxia was marked in heart, slight in kidney medulla and undetectable in the other organs, indicating that the apoptotic pathway may be triggered by HIF-1a-independent mechanisms. These data emphasize that the array of responses elicited by inadequate O2 supply with respect to needs is very specific for each tissue and cell.