Background: 

Hearts (H) with streptozotocin (STZ) diabetes (DIA) are pseudo-hypoxic due to decreased capability of mitochondria (MIT) to utilise oxygen. However, besides pathological alterations they also exhibit compensatory and adaptation changes.

Aims: 

i) Elucidation of mechanisms and outcome of STZ-DIA-induced functional alterations in H-MIT; ii) Investigation of signals by which DIA-H-MIT may crosstalk with other subcellular organells and modulate the expression of hypoxic genes. Experimental: DIA induced in male Wistar rats (220 + 20 g b. wt.) by 65 mg.kg^-1 STZ i.p., was terminated on 8^th day after STZ application. MIT were isolated by differential centrifugation + protease. Estimations: MIT function, MIT-NO-synthase, conjugated dienes and membrane fluidity. MIT-signaling towards hypoxic genes (carbonic anhydrase, CA IX expression by RT PCR) was studied with diazoxide (DZO), tempol (TL), N-acetylcystein (NAC) etc., as modulators.

Results and Discussion: 

DIA represented by increase in blood glucose, glycohemoglobin, triacylglycerols, cholesterol and decrease in insulin: +235.8, +89.5, +270.4, +53.6 and -53.9% resp. MIT O₂ consumption, phosphorylation rate and NO synthase activity were also decreased (p < 0.05), but energy transport from MIT to the cytoplasma was facilitated. DZO and TL stimulated CA IX expression, the former via inhibition of succinate oxidation followed by its efflux from the MIT, the latter may be by acting as prooxidant. NAC as antioxidant and BA as inhibitor of ROS release from MIT prevented CA IX expression.

Conclusions: 

Release of succinate and radicals from functionally remodeled DIA-H-MIT represent signals for expression of hypoxic genes in the myocardium. Increased NO-signaling was not confirmed.

Grants: APVV 51-027404, 51-017902; VEGA 2/7126/27; NATO CBP.NUKR. CLG 981884.