ABSTRACT
Arterial injury after orthopedic procedures is an uncommon complication that can present clinically in a variety of forms and has conventionally been repaired by open vascular surgery. The case and discussion in this article highlights the usefulness of endovascular repair following a delayed presentation of vascular injury from an orthopedic procedure.
Subject(s)
Aneurysm, False/surgery , Balloon Occlusion , Blood Vessel Prosthesis Implantation/instrumentation , Femoral Artery/surgery , Fracture Fixation, Internal/adverse effects , Iatrogenic Disease , Stents , Aged, 80 and over , Aneurysm, False/diagnostic imaging , Aneurysm, False/etiology , Female , Femoral Artery/diagnostic imaging , Humans , Radiography , Treatment OutcomeABSTRACT
The oxidative stress hypothesis of aging predicts that a reduction in the generation of mitochondrial reactive oxygen species (ROS) will decrease oxidative damage and extend life span. Increasing mitochondrial proton leak-dependent state 4 respiration by increasing mitochondrial uncoupling is an intervention postulated to decrease mitochondrial ROS production. When human UCP2 (hUCP2) is targeted to the mitochondria of adult fly neurons, we find an increase in state 4 respiration, a decrease in ROS production, a decrease in oxidative damage, heightened resistance to the free radical generator paraquat, and an extension in life span without compromising fertility or physical activity. Our results demonstrate that neuronal-specific expression of hUCP2 in adult flies decreases cellular oxidative damage and is sufficient to extend life span.
Subject(s)
Membrane Transport Proteins/biosynthesis , Mitochondrial Proteins/biosynthesis , Nervous System/metabolism , Neurons/metabolism , Animals , Animals, Genetically Modified , Blotting, Western , DNA, Complementary/metabolism , Drosophila melanogaster , Female , Humans , Hydrogen Peroxide/chemistry , Ion Channels , Longevity , Male , Mitochondria/metabolism , Oxidative Stress , Oxygen Consumption , Reactive Oxygen Species , Sex Factors , Time Factors , Uncoupling Protein 2ABSTRACT
Sequence alignment of conserved signature motifs predicts the existence of the uncoupling protein 5 (UCP5)/brain mitochondrial carrier protein (BMCP1) homologue in Drosophila melanogaster. Here we demonstrate the functional characterization of the Drosophila melanogaster UCP5 protein (DmUCP5) in the heterologous yeast system, the first insect UCP reported to date. We show that physiological levels of DmUCP5 expression are responsible for an increase in state 4 respiration rates and a decrease in mitochondrial membrane potential. Furthermore, similar to UCP1, UCP2, and UCP3, the uncoupling activity of DmUCP5 is augmented by fatty acids and inhibited by the purine nucleotide GDP. Thus, DmUCP5 shares the mechanisms known to regulate the UCPs characterized to date. A lack of growth inhibition observed in DmUCP5 expressing yeast is consistent with the notion that physiological uncoupling has a minimal effect on cell growth. Finally, semiquantitative RT-PCR analysis shows a distinctive pattern of DmUCP5 expression predominantly localized in the adult head, similar to the expression pattern of its mammalian homologues. The conserved regulation of the expression of this gene from mammals to fruit flies suggests a role for UCP5 in the brain.
