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

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Abstract

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.

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Authors and Affiliations

  1. Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal

    Susana Cardoso, Maria S. Santos, António Moreno & Paula I. Moreira

  2. Department of Life Sciences – Faculty of Sciences and Technology, University of Coimbra, 3004-517, Coimbra, Portugal

    Susana Cardoso, Maria S. Santos & António Moreno

  3. Institute of Marine Research, University of Coimbra, 3004-517, Coimbra, Portugal

    António Moreno

  4. Laboratory of Physiology, Faculty of Medicine, University of Coimbra, 3004-548, Coimbra, Portugal

    Paula I. Moreira

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  1. Susana Cardoso
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  2. Maria S. Santos
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  3. António Moreno
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  4. Paula I. Moreira
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Correspondence to Paula I. Moreira.

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Cardoso, S., Santos, M.S., Moreno, A. et al. UCP2 and ANT differently modulate proton-leak in brain mitochondria of long-term hyperglycemic and recurrent hypoglycemic rats. J Bioenerg Biomembr 45, 397–407 (2013). https://doi.org/10.1007/s10863-013-9503-2

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  • DOI: https://doi.org/10.1007/s10863-013-9503-2

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