Multiple effects of hyperbaric oxygen on the expression of HIF-1 alpha and apoptotic genes in a global ischemia-hypotension rat model.

Abstract

Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor specifically activated by hypoxia. Activation of proapoptotic caspase-9 and caspase-3 pathways, by binding with tumor suppressor p53, HIF-1alpha could lead to harmful actions such as apoptosis. We examined whether increasing oxygen levels by hyperbaric oxygen (HBO) offers neuroprotection, at least partially by suppression of HIF-1alpha and apoptotic genes. Male SD rats (n = 78) were randomly divided into 13 groups: 1 sham group, 6 groups of global ischemia-hypotension (GI), and 6 groups of HBO treatment after global ischemia-hypotension (GI + HBO). HBO (3 ATA for 2 h) was applied at 1 h after global ischemia-hypotension. Rats were sacrificed at 6, 12, 24, 48, and 96 h and 7 days. Global ischemia-hypotension (10 min ischemia, 30-35 mm Hg) produced a marked increase of HIF-1alpha expressions in the hippocampus and cortex at 6 h and peaked at 48-96 h. The expressions of p53, caspase-9, and caspase-3 were all increased in a similar time course. These molecular changes were accompanied by massive cell loss in the hippocampal regions and to a lesser degree in the cortex, with features of apoptosis. HBO treatment reduced expressions of HIF-1alpha, p53, caspase-9, and caspase-3 and decreased cell death. The protein levels of proapoptotic caspase-8 and antiapoptotic bcl-2 were increased after global ischemia-hypotension and HBO potentiated the expression of caspase-8 and decreased expression of bcl-2. These results indicate that HBO has multiple actions on apoptotic genes even though the overall effect of HBO was decreased HIF-1alpha expression and reduced apoptosis after global ischemia-hypotension.

• Authors: Yun Li, Changman Zhou, John W Calvert, Austin R T Colohan, John H Zhang
• Journal: Experimental neurology (Exp Neurol) Vol. 191 Issue 1 Pg. 198-210 (Jan 2005) ISSN: 0014-4886 [Print] United States
• PMID: 15589527 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• Transcription Factors

Topics

• Animals
• Apoptosis (genetics)
• Brain Ischemia (genetics, metabolism, therapy)
• Disease Models, Animal
• Gene Expression Regulation (physiology)
• Hyperbaric Oxygenation (methods)
• Hypotension (genetics, metabolism, therapy)
• Hypoxia-Inducible Factor 1, alpha Subunit
• Male
• Rats
• Rats, Sprague-Dawley
• Transcription Factors (biosynthesis, genetics)