nNOS-alpha up-regulation and translocation into mitochondria contribute to hypothyroid phenotype.

FRANCO MC; ANTICO ARCIUCH V; PERALTA JG; PODEROSO JJ; CARRERAS MC

Aguas de Lindoia, Brasil

Congreso; IV Meeting of the South American Group of the Society for Free Radical Biology and Medicine; 2005

South American Group of the Society for Free Radical Biology and Medicine

Variations in thyroid status are followed by changes in mitochondrial activities and oxygen uptake. We analized here the effects of mtNOS regulation by hypothyroidism on the respiratory chain and cellular redox metabolism. Male Wistar rats were separeted in 4 groups: Control (C), Hypothyroid (Hypo; methimazole 0.02%, 4 wk), Hypo+T3 (Hypo+1 IP injection of 15 µg T3/kg, 3 d) and Hypo+L-NAME (Hypo+0.75 mg/ml of L-NAME the last 3 wk). TSH levels were > 80 ng/ml in Hypo and Hypo+L-NAME and were normalized by T3 administration (11 ng/ml). Basal metabolic rate was 31% lower in Hypo than C, and was restored by T3 or L-NAME administration. In Hypo, there was 2-fold increase of nNOS mRNA and protein levels, in parallel with nNOS translocation into mitochodria. Besides, there was a 4-fold increase of O2- in hypo respect to C; at the same mtNOS content, L-NAME completely prevented these effects. Protein nitration was higher in Hypo than C, mainly in complex I, that maintained only 38% of activity. The interaction between mtNOS and complex I proteins (tested by co-immunoprecipitation) could facilitate these effects. Conclusions: the increase of nNOS and its subsequent translocation into mitochondria in the hypothyroid condition, lead to an increase in reactive oxygen species production and inhibition of complex I activity due to protein nitration, that may be facilitated by the interaction between mtNOS and proteins of complex I.