Up-regulation of avian uncoupling protein in cold-acclimated and hyperthyroid ducklings prevents reactive oxygen species production by skeletal muscle mitochondria

Abstract

BackgroundAlthough identified in several bird species, the biological role of the avian homolog of mammalian uncoupling proteins (avUCP) remains extensively debated. In the present study, the functional properties of isolated mitochondria were examined in physiological or pharmacological situations that induce large changes in avUCP expression in duckling skeletal muscle.ResultsThe abundance of avUCP mRNA, as detected by RT-PCR in gastrocnemius muscle but not in the liver, was markedly increased by cold acclimation (CA) or pharmacological hyperthyroidism but was down-regulated by hypothyroidism. Activators of UCPs, such as superoxide with low doses of fatty acids, stimulated a GDP-sensitive proton conductance across the inner membrane of muscle mitochondria from CA or hyperthyroid ducklings. The stimulation was much weaker in controls and not observed in hypothyroid ducklings or in any liver mitochondrial preparations. The production of endogenous mitochondrial reactive oxygen species (ROS) was much lower in muscle mitochondria from CA and hyperthyroid ducklings than in the control or hypothyroid groups. The addition of GDP markedly increased the mitochondrial ROS production of CA or hyperthyroid birds up to, or above, the level of control or hypothyroid ducklings. Differences in ROS production among groups could not be attributed to changes in antioxidant enzyme activities (superoxide dismutase or glutathione peroxidase).ConclusionThis work provides the first functional in vitro evidence that avian UCP regulates mitochondrial ROS production in situations of enhanced metabolic activity.

The 12-day thermoregulatory metamorphosis of Red-winged Blackbirds (Agelaius phoeniceus)

“…Researchers have confirmed the relationship of avUCP and ROS production by demonstrating that down-regulation of avUCP results in an increase of mitochondrial ROS and more oxidative damage and vice versa (Mujahid et al 2006(Mujahid et al , 2007(Mujahid et al , 2009. Expression patterns of avUCP in coldacclimated ducklings suggest that skeletal muscle avUCP expression helps to regulate ROS production associated with increased metabolism (Rey et al 2010). The rise in avUCP is associated with an increase in the ANCOVA mass adjusted V o 2 that occurs between 3 and 7 dph (Table 2) and may be important for regulating ROS as metabolism and associated thermogenic capacity increases.…”

Alteration of mitochondrial efficiency affects oxidative balance, development and growth in frog (Rana temporaria) tadpoles

“…During oxidative phosphorylation processes, the rate of mitochondrial ROS generation is strongly sustained by a reduced state of the electron transport chain and a high inner membrane potential (Boveris et al, 1976;Korshunov et al, 1997;Barja, 2007). Hence, an increased proton flux across the inner membrane via the F 0 F 1 -ATP synthase (state 3 respiration) or other proton leak pathways such as uncoupling proteins or mitochondrial uncouplers, including the protonophore 2,4-dNP, would attenuate ROS production by lowering the membrane potential (Korshunov et al, 1997;Brand, 2005;Rey et al, 2010). The decreased ROS generation found in 2,4-dNP-treated tadpoles is thus in accordance with previously reported data in isolated mitochondria, organs or whole animals (Okuda et al, 1992;Batandier et al, 2006;da Silva et al, 2008).…”

The evolution of endothermy is explained by thyroid hormone-mediated responses to cold in early vertebrates

“…Thyroid hormone also induces mitochondrial uncoupling by promoting the expression of uncoupling proteins in mammals, which facilitate proton leak through the mitochondrial membrane and thereby heat production (van den Berg et al, 2011). Similarly, in birds, uncoupling protein expression is decreased with hypothyroidism, although uncoupling proteins are more likely to be associated with reactive oxygen species defence rather than heat production (Rey et al, 2010;Walter and Seebacher, 2009).…”

“…Thyroid hormone also induces mitochondrial uncoupling by promoting the expression of uncoupling proteins in mammals, which facilitate proton leak through the mitochondrial membrane and thereby heat production (van den Berg et al, 2011). Similarly, in birds, uncoupling protein expression is decreased with hypothyroidism, although uncoupling proteins are more likely to be associated with reactive oxygen species defence rather than heat production (Rey et al, 2010;Walter and Seebacher, 2009).Additionally, in mammals, thyroid hormone interacts with the hypothalamus to modulate sympathetic activity and thereby β-adrenergic receptor-induced heat production in brown adipose tissue and skeletal muscle, as well as heart rate and cardiac output (Cannon and Nedergaard, 2004; Carr and Kranias, 2002). These effects of thyroid hormone on sympathetic tone of the heart in mammals are mirrored in zebrafish, where increased sympathetic output results in improved cardiac performance under cold conditions.…”