UCP2 and ANT differently modulate proton-leak in brain mitochondria of long-term hyperglycemic and recurrent hypoglycemic rats

作者：Cardoso Susana; Santos Maria S; Moreno Antonio; Moreira Paula I^*

来源：Journal of Bioenergetics and Biomembranes, 2013, 45(4): 397-407.

DOI：10.1007/s10863-013-9503-2

• ANT
• Cortical brain mitochondria
• Long-term hyperglycemia
• Proton-leak
• Recurrent hypoglycemia
• UCP2

A growing body of evidence suggests that mitochondrial proton-leak functions as a regulator of reactive oxygen species production and its modulation may limit oxidative injury to tissues. The main purpose of this work was to characterize the proton-leak of brain cortical mitochondria from long-term hyperglycemic and insulin-induced recurrent hypoglycemic rats through the modulation of the uncoupling protein 2 (UCP2) and adenine nucleotide translocator (ANT). Streptozotocin-induced diabetic rats were treated subcutaneously with twice-daily insulin injections during 2 weeks to induce the hypoglycemic episodes. No differences in the basal proton-leak, UCP2 and ANT protein levels were observed between the experimental groups. Mitochondria from recurrent hypoglycemic rats presented a decrease in proton-leak in the presence of GDP, a specific UCP2 inhibitor, while an increase in proton-leak was observed in the presence of linoleic acid, a proton-leak activator, this effect being reverted by the simultaneous addition of GDP. Mitochondria from long-term hyperglycemic rats showed an enhanced susceptibility to ANT modulation as demonstrated by the complete inhibition of basal and linoleic acid-induced proton-leak caused by the ANT specific inhibitor carboxyatractyloside. Our results show that recurrent-hypoglycemia renders mitochondria more susceptible to UCPs modulation while the proton-leak of long-term hyperglycemic rats is mainly modulated by ANT, which suggest that brain cortical mitochondria have distinct adaptation mechanisms in face of different metabolic insults.

• 出版日期2013-8