Uncoupling Agents

Publication Title: 
IUBMB life

In Roman mythology, Janus was the god of gates, doors, beginnings and endings. He was usually depicted with two faces looking in opposite directions. Janus was frequently used to symbolize change and transitions, such as the progression from past to future or from one viewpoint to another. 2,4-dinitrophenol (DNP) and other nitrophenols have long been known to be toxic at high concentrations (the 'bad' face of DNP), an effect that appears essentially related to interference with cellular energy metabolism due to uncoupling of mitochondrial oxidative phosphorylation.

De Felice, Fernanda G.
Ferreira, SÈrgio T.
Publication Title: 
The International Journal of Biochemistry & Cell Biology

Calorie-restricted feeding retards the rate of ageing in mammalian and invertebrate species. The molecular mechanisms underlying this effect include a lower rate of accrual of tissue oxidative damage that is associated with a significantly lower rate of mitochondrial free radical generation in rodent species. To identify the important sites of control and regulation for mitochondrial free radical generation during ageing and calorie-restricted feeding, metabolic control analysis is being applied to the study of mitochondrial bioenergetics.

Merry, B. J.
Publication Title: 
Cell Metabolism

Age-related disease, not aging per se, causes most morbidity in older humans. Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression diminishes age-related disease in three mouse models. In a longevity study, median survival was increased in UCP mice (animals with skeletal muscle-specific UCP1 expression), and lymphoma was detected less frequently in UCP female mice. In apoE null mice, a vascular disease model, diet-induced atherosclerosis was decreased in UCP animals.

Gates, Allison C.
Bernal-Mizrachi, Carlos
Chinault, Sharon L.
Feng, Chu
Schneider, Jochen G.
Coleman, Trey
Malone, James P.
Townsend, R. Reid
Chakravarthy, Manu V.
Semenkovich, Clay F.
Publication Title: 
Journal of Molecular and Cellular Cardiology

C-reactive protein (CRP), a cardiovascular risk marker, induces endothelial dysfunction. We have previously shown that CRP decreases endothelial nitric oxide synthase (eNOS) expression and bioactivity in human aortic endothelial cells (HAECs). In this study, we examined the mechanisms by which CRP decreases eNOS activity in HAECs. To this end, we explored different strategies such as availability of tetrahydrobiopterin (BH4)-a critical cofactor for eNOS, superoxide (O(2)(-)) production resulting in uncoupling of eNOS and phosphorylation/dephosphorylation of eNOS.

Singh, Uma
Devaraj, Sridevi
Vasquez-Vivar, Jeannette
Jialal, Ishwarlal
Publication Title: 
Brain Research

Parkinson's disease (PD) is a movement disorder caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to nigrostriatal degeneration. The inhibition of mitochondrial respiratory chain complex I and oxidative stress-induced damage have been implicated in the pathogenesis of PD. The present study used these specific mitochondrial complex I inhibitors (rotenone and 1-methyl-4-phenylpyridinium or MPP(+)) on striatal and cortical neurons in culture.

Ying, Rong
Liang, Huan Ling
Whelan, Harry T.
Eells, Janis T.
Wong-Riley, Margaret T. T.
Publication Title: 
Aging Cell

Caloric restriction is the most effective non-genetic intervention to enhance lifespan known to date. A major research interest has been the development of therapeutic strategies capable of promoting the beneficial results of this dietary regimen. In this sense, we propose that compounds that decrease the efficiency of energy conversion, such as mitochondrial uncouplers, can be caloric restriction mimetics.

Caldeira da Silva, Camille C.
Cerqueira, Fernanda M.
Barbosa, Lívea F.
Medeiros, Marisa H. G.
Kowaltowski, Alicia J.
Publication Title: 
Toxicological Sciences: An Official Journal of the Society of Toxicology

Berberine [Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo (5,6-a) quinolizinium] is an alkaloid present in plants of the Berberidaceae family and used in traditional Chinese and North American medicine. We have previously demonstrated that berberine causes mitochondrial depolarization and fragmentation, with simultaneous increase in oxidative stress. We also demonstrated that berberine causes an inhibition of mitochondrial respiration and a decrease on calcium loading capacity through induction of the mitochondrial permeability transition (MPT).

Pereira, Cláudia V.
Machado, Nuno G.
Oliveira, Paulo J.
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