Meeting Abstract
P3.2 Tuesday, Jan. 6 Nitric Oxide-mediated Angiogenesis in Antarctic Icefish? BORLEY, K.A.*; SIDELL, B.D.; University of Maine kimberly.borley@maine.edu
Nitric oxide (NO), produced by nitric oxide synthase, regulates diverse processes including angiogenesis and mitochondrial biogenesis. NO rapidly degrades in most vertebrates by reaction with hemoglobin (Hb) and myoglobin (Mb). Antarctic icefish completely lack Hb. In the absence of Hb, we hypothesize that NO accumulates to higher steady-state concentration. This may trigger high cardiac mitochondrial density and dense retinal vasculature observed in these fish. We measured breakdown products of NO (NO2– and NO3–) in plasma of Hb and +Hb Antarctic notothenioids. Aggregate [NO2–+ NO3–] are higher in plasma of Hb icefish (C. aceratus: 22.75 +/- 1.15M) than in a red-blooded notothenioid (N. coriiceps: 14.66 +/- 0.67M), indicating that NO concentrations are higher in white-blooded fish than +Hb fish. To evaluate whether NO stimulates angiogenesis in white-blooded fish, we used quantitative PCR (Q-PCR) to measure expression of genes involved in angiogenesis in Hb and +Hb notothenioids. We found no significant differences in expression of hypoxia inducible factor-1α (HIF-1α) or vascular endothelial growth factor (VEGF). These results suggest that, if loss of Hb stimulates angiogenesis in icefish, the process must occur early in development and is not upregulated in adults. To further test relationships among [Hb], [NO] and angiogenesis, we treated red-blooded notothenioids with phenylhydrazine (PHZ), a potent hemolytic agent. Hematocrit of fish treated with PHZ for 10 days decreased from ~37% to less than 5% while [NO2–+ NO3–] increased concomitantly (N. coriiceps: 14.66 +/- 0.67M, N. coriiceps + PHZ: 19.60 +/- 1.18M, p=0.01). Expression of PHD2 (prolyl hydroxylase domain protein-2), HIF-1α and VEGF, known angiogenic factors, significantly increases in PHZ-treated N. coriiceps. Supported by NSF grants ANT 04-37887 and 07-39637.
