Age-related differences in hypoxia-associated genes and cytokine profile in male Wistar rats

Abstract

Hypoxia tolerance of the organism depends on many factors, including age. High newborn organisms tolerance and high level of oxidative stress throughout aging were demonstrated by many studies. However, there is lack of investigations reflecting the expression of key hypoxia-inducible factor HIF in different age organisms in correlation to levels of pro-inflammatory and anti-inflammatory cytokines. Liver is a sensitive to hypoxia organ, and is an important organ in providing an acute reaction to infections – it synthesizes acute inflammation phase proteins, in particular, C-reactive protein. The aim of study was to determine relationship between age-related tolerance to hypoxia and HIF-1 and PHD2 (prolyl hydroxylase domain protein) expression levels in the liver and the production of cytokines in the spleen in newborn, prepubertal and adult Wistar rats. Newborn rats are characterized by high mRNA Hif-1α expression level in the liver, accompanied by a low content of HIF-1 protein and high level of PHD2. The growth in HIF-1α protein level throughout age is accompanied by the growth of pro-inflammatory cytokines level. Prepubertal animals are the least hypoxia resistant and their HIF-1α mRNA expression level was higher than in adult animals. The PHD2 activity in prepubertal animals was significantly reduced in comparison to newborn rats, and the HIF-1α protein level did not change. Further studies require the identification of additional mechanisms, determining the regulation of the HIF-1α level in prepubertal animals.