UCP1 and defense against oxidative stress. 4-Hydroxy-2-nonenal effects on brown fat mitochondria are uncoupling protein 1-independent.
Uncoupling proteins have been ascribed a role in defense against oxidative stress, particularly by being activated by products of oxidative stress such as 4-hydroxy-2-nonenal (HNE). We have investigated here the ability of HNE to activate UCP1. Using brown fat mitochondria from UCP1+/+ and UCP1-/- mice to allow for identification of UCP1-dependent effects, we found that HNE could neither (re)activate purine nucleotide-inhibited UCP1, nor induce additional activation of innately active UCP1. The aldehyde nonenal had a (re)activating effect only if converted to the corresponding fatty acid by aldehyde dehydrogenase; the presence of a carboxyl group was thus an absolute requirement for (re)activation. The UCP1-dependent proton leak was not increased by HNE but HNE changed basal proton leak characteristics in a UCP1-independent manner. In agreement with the in vitro results, we found, as compared with UCP1+/+ mice, no increase in HNE/protein adducts in brown fat mitochondria isolated from UCP1-/- mice, irrespective of whether they were adapted to thermoneutral temperature (30 degrees C) or to the cold (4 degrees C). The absence of oxidative damage in UCP1-/- mitochondria was not due to enhanced activity of antioxidant enzymes. Thus, HNE did not affect UCP1 activity, and UCP1 would appear not to be physiologically involved in defense against oxidative stress. Additionally, it was concluded that at least in brown adipose tissue, conditions of high mitochondrial membrane potential, high oxygen tension, and high substrate supply do not necessarily lead to increased oxidative damage.
Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
Irina G
IG
Shabalina
Natasa
N
Petrovic
Tatiana V
TV
Kramarova
Joris
J
Hoeks
Barbara
B
Cannon
Jan
J
Nedergaard
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005260:Female; D007473:Ion Channels; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D018384:Oxidative Stress; D010101:Oxygen Consumption; D000071256:Uncoupling Protein 1
D000447:Aldehydes; D000975:Antioxidants; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C027576:4-hydroxy-2-nonenal