Exclusive neuronal expression of SUCLA2 in the human brain

SUCLA2 encodes the ATP-forming subunit (A-SUCL-) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here we show that immunoreactivity of A-SUCL- in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a fluorescent Nissl dye. A-SUCL- immunoreactivity co-localized >99% with that of the d subunit of the mitochondrial F0-F1 ATP synthase. Specificity of the anti-A-SUCL- antiserum was verified by the absence of labeling in fibroblasts from a patient with a complete deletion of SUCLA2. A-SUCL- immunoreactivity was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming subunit (G-SUCL-) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL- immunoreactivity that was however, not upregulated in samples obtained from diabetic versus non-diabetic patients, as has been described for murine brain. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

Aging, Estrogen Loss and Epoxyeicosatrienoic Acids (EETs)

Inflammation is a key element in many cardiovascular diseases. Both estrogen loss, caused by menopause, and aging have inflammatory consequences. Epoxyeicosatrienoic acids (EETs) are anti-inflammatory molecules synthesized by various cytochrome P450 (Cyp) enzymes from arachidonic acid. EETs are in the third (Cytochrome P450) pathway of arachindonic acid metabolism, others being cyclooxygenases and lipoxygenases. We hypothesized that aging and estrogen loss would reduce levels of anti-inflammatory EETs. Adult (6 mo) and aged (22 mo) ovariectomized rats with (OP) and without (Ovx) 17-∃-estradiol replacement were used in this study. Mass spectrometry was used to measure levels of EETs and their metabolites, dihydroxyeicosatrienoic acids (DHETs). Levels of Cyp2C2, Cyp2C6, and Cyp2J2, the principal Cyps responsible for EETs synthesis, as well as soluble epoxide hydrolase (sEH), which metabolizes EETS to DHETs, were determined via western blot. Overall Cyp levels decreased with age, though Cyp2C6 increased in the liver. sEH was increased in the kidney with estrogen replacement. Despite protein changes, no differences were measured in plasma or aortic tissue levels of EETs. However, plasma 14,15 DHET was increased in aged Ovx, and 5,6 DHET in adult OP. In conclusion neither aging nor estrogen loss decreased the anti-inflammatory EETs in the cardiovascular system