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AbstractWe studied liver oxidative capacity and O 2 consumption in hypothyroid rats treated for 10 days with T 4 , or T 3 , or treated for 10 days with T 3 and exposed to cold for the last two days. The metabolic response of homogenates and mitochondria indicated that all treatments increased the synthesis of respiratory chain components, whereas only the cold induced mitochondrial proliferation. Determination of mRNA and protein expression of transcription factor activators, such as NRF-1 and NRF-2, and coactivators, such as PGC-1, showed that mRNA levels, except PGC-1 ones, were not related to aerobic capacities. Conversely, a strong correlation was found was between cytochrome oxidase activity and PGC-1 or NRF-2 protein levels.Such a correlation was not found for NRF-1. Our results strongly support the view that in rat liver PGC-1 and NRFs are responsible for the iodothyronine-induced increases in respiratory chain components, whereas their role in cold-induced mitochondrial proliferation needs to be further on clarified.
SUMMARYWe compared the changes in tissue aerobic metabolism and oxidative damage elicited by hypothyroid rat treatment with T 3 and its analog GC-1. Aerobic capacities, evaluated by cytochrome oxidase activities, were increased more by T 3 than by GC-1. Furthermore, the response of the tissues to T 3 was similar, whereas the response to GC-1 was high in liver, low in muscle and scarce in heart. Both treatments induced increases in ADP-stimulated O 2 consumption, which were consistent with those in aerobic capacities. However, unlike T 3 , GC-1 differentially affected pyruvate/malate-and succinate-supported respiration, suggesting that respiratory chain components do not respond as a unit to GC-1 stimulation. According to the positive relationship between electron carrier levels and rates of mitochondrial generation of oxidative species, the most extensive damage to lipids and proteins was found in T 3 -treated rats. Examination of antioxidant enzyme activities and scavenger levels did not clarify whether oxidative damage extent also depended on different antioxidant system effectiveness. Conversely, the analysis of parameters determining tissue susceptibility to oxidants showed that pro-oxidant capacity was lower in GC-1-than in T 3 -treated rats, while antioxidant capacity was similar in treatment groups. Interestingly, both agonists decreased serum cholesterol levels, but only GC-1 restored euthyroid values of heart rate and indices of tissue oxidative damage, indicating that GC-1 is able to lower cholesterolemia, bypassing detrimental effects of T 3 .
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