Introduction
HIF-beta subunits are stable regardless of oxygen
concentration and constitutively translocate to the nucleus. It was
shown previously that HIF-1beta protein expression is nearly
ubiquitous in newborn kidney and that HIF-1beta dimerizes with
either HIF-1alpha or -2alpha. Here it is shown that aryl hydrocarbon
receptor nuclear transporter-2 (ARNT2/HIF-2beta) also
heterodimerized with HIF-1alpha and -2alpha. ARNT2/HIF-2beta protein
was highly expressed in newborn kidney but decreased significantly
with age, whereas HIF-1beta levels remained relatively constant. By
immunohistochemical analysis, widespread expression of HIF-1beta was
observed in developing and mature kidneys. ARNT2/HIF-2beta protein
distribution was restricted to distal segments of developing
nephrons and in mature kidney was confined specifically to thick
ascending limb of Henle's loop. The data presented here suggest that
ARNT2/HIF-2beta is required at high levels during nephrogenesis in
distal tubules and later exclusively in thick ascending limb.
Furthermore, Hypoxyprobe-1 and lotus lectin co-localization studies
showed that developing proximal convoluted tubules were the most
severely hypoxic nephron segment in immature kidney. Because
HIF-2beta protein was not abundantly expressed in this segment, it
may not be engaged in mediating responses to severe hypoxia.
PMID: 15466261
Northern analyses showed that dHIF-1alpha and
dHIF-1beta expressed their highest level at an embryonic stage. From
the pupal stage on, their expression was sharply reduced and
maintained at a steady level. Anoxia treatment up-regulated the
expression of the both alpha and beta subunits. Over-expression of
dHIF-1alpha in transgenic embryos resulted in embryonic lethality,
while over-expression of dHIF-1beta significantly prolonged fly
recovery time from a 5-min anoxic stupor. The cloning and
characterization dHIF-1beta reported in this paper provide a
framework for further genetic dissection of the HIF-1 complex in its
role in the cellular or tissue response to O(2) deprivation.
PMID: 10581393
zinc induced the accumulation and nuclear translocation of hypoxia-inducible factor (HIF)-1alpha but inhibited the nuclear translocation of HIF-1beta, which inactivated HIF-1 and suppressed EPO mRNA induction in hypoxic cells. PMID: 10679259