Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two-dimensional gel electrophoresis of acidic and basic [35S]methionine-labeled polypeptides derived from primary cultures of human retinal-pigment epithelial cells revealed about 850 proteins. By co-electrophoresis with highly purified, evolutionally conserved proteins, alpha-actinin, calmodulin, cytosol retinal-binding protein, alpha- and beta-tubulin, and vinculin (mass: 130 000 Da) were tentatively identified in the fluorograms. Quantification of greater than 100 of the excised radioactive spots by liquid scintillation counting revealed an estimated overall gel/gel and donor/donor variation of 40% (SEM, 21%), the latter for data on three to four donors 57 to 81 years old. Therefore, for a difference from normal to be significant (p less than or equal to 0.01), it would, on average, have to exceed 88% of the control mean for that protein. Putative glycoproteins were independently radiolabeled, with tritiated sugars as precursors. Glucosamine was incorporated most rapidly and with the highest specific activity. It labeled about 170 polypeptides. Fucose and N-acetylmannosamine, respectively, labeled 74 and 27 polypeptides. The glycoprotein label was maximal in about 16 very acidic proteins with apparent molecular masses between 50 000 and 150 000 Da. Parallel use of both a sugar and an amino acid label facilitates identification of proteins in two-dimensional gels.
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PMID:Two-dimensional electrophoresis of proteins from cultured human retinal-pigment epithelial cells: internal references, cataloging, and glycoproteins. 649 66

The decrease in Ca2+ responsiveness of myofilaments in stunned myocardium implies that there may be structural changes in proteins composing the contractile machinery. To elucidate the lesion in stunned myocardium, isolated guinea pig hearts were subjected to global ischemia at 37 degrees C and reperfused. SDS-PAGE revealed that the contents of desmin, alpha-actinin, and spectrin decreased in the myofibrillar fraction isolated from hearts reperfused after 60-minute ischemia compared with nonischemic control hearts. To examine the change of cytoskeletal proteins in stunned myocardium, immunohistochemical studies with antibodies against these proteins were performed after 15 minutes of ischemia. In stunned myocardium, the staining was largely intact, but there were some lesions where desmin was not stained and alpha-actinin and spectrin were only weakly identified. The percentage of normally stained areas in the myocardium (percent stained area), quantified by image processing, was significantly lower in stunned myocardium (79.6 +/- 3.6%, mean +/- SEM) than in nonischemic control myocardium (96.5 +/- 0.7%). Percent recovery of developed pressure significantly correlated with percent stained area (r = .82, P < .001). In hearts subjected to 15-minute ischemia but not reperfused, or in hearts reperfused with Ca(2+)-free solution after 15-minute ischemia, staining by the antibodies remained intact, suggesting that the change of the cytoskeletal proteins is mediated by Ca2+ overload during reperfusion. In hearts treated with the protease inhibitor leupeptin (50 mumol/L) or calpain inhibitor I (100 mumol/L), both developed pressure and staining were well preserved. These results indicate that contractile dysfunction in stunned myocardium has a strong correlation with the disappearance of cytoskeletal proteins that may be mediated by a Ca(2+)-dependent intracellular protease activated during reperfusion. The disruption of cytoskeletal proteins is a possible mechanism for stunning, although it may be a secondary effect of protease activation.
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PMID:Inhomogeneous disappearance of myofilament-related cytoskeletal proteins in stunned myocardium of guinea pig. 878 78

The Z-disk protein alpha-actinin-3 is only expressed in type II muscle fibres, which are responsible for generating forceful contractions at high velocity. Despite the evolutionary conservation of alpha-actinin-3, approximately one in every five Caucasians of European ancestry is totally deficient in this protein, due to homozygosity for a R577X polymorphism in the ACTN3 gene. This, together with the results of recent research on elite athletes, suggests that the "null" XX polymorphism might confer some advantage to endurance performance events. To test this hypothesis, we studied the frequency distribution of R577X genotypes in a group of 50 top-level male professional cyclists (26.9 +/- 0.4 yrs [mean +/- SEM]; VO2max: 73.5 +/- 0.8 ml x kg (-1) x min (-1)). Their results were compared with those of a group of 52 Olympic-class male endurance runners (26.8 +/- 0.6 yrs; VO2max: 73.3 +/- 0.8 ml x kg (-1) x min (-1)) and 123 healthy, sedentary male controls. All subjects were Caucasian, and of European ancestry. No significant differences (p > 0.05) were found between groups: RR: 28.5 %; RX: 53.6 % and XX: 17.9 % in controls; RR: 28.0 %; RX: 46.0 % and XX: 26.0 % in cyclists; and RR: 25.0 %; RX: 57.7 %; XX: 17.3 % in runners). No differences were found in indices of endurance performance (VO2peak or ventilatory thresholds) between athlete carriers of each R577X genotype. In summary, although the alpha-actinin-3 deficient XX genotype may be detrimental for sprint performance in humans, the R577X polymorphism of the ACTN3 gene does not appear to confer an advantage on the ability of male athletes to sustain extreme endurance performance.
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PMID:ACTN3 genotype in professional endurance cyclists. 1661 41

We have previously shown that cells isolated from the outer ears of adult mice are a source of mesenchymal stem cells that can be induced to differentiate into adipo-, osteo-, and chondrocytes. In this study, we demonstrate that ear mesenchymal stem cells (EMSC) express stromal cell-associated markers (CD44, CD73) and stem cell marker Sca-1 and can be differentiated into spontaneously contracting muscle cells. Treatment of cells with epidermal growth factor (EGF) change their morphology from fibroblast shapes into stick-like structures that show repeated spontaneous contractions. Under conditions that promote myogenic differentiation, EMSC expressed mRNA for myoD and ventricular specific myosin light chain (MLC-2v) and protein for connexin 43, sarcomeric alpha-actinin, myocyte enhancer factor 2c (MEF2c), myosin heavy chain (MyHC), myogenin, and sarco-endoplasmic reticulum Ca(2+)ATPase (SERCA) 1. However, the cells were negative for Nkx2.5, GATA4, and ANP. Intracellular Ca(2+) transients in spontaneously beating EMSC, visualized by Fluo-3AM, showed a frequency of Ca(2+) oscillations ranging over 28-59/min (mean 41.17 +/- SEM 1.54). We also demonstrated that small pieces of ear tissues (ear punches) collected from live mice provide sufficient numbers of EMSC to isolate, culture and differentiate them into myocytes. Due to the ease of acquiring an expanding repertoire of differentiated EMSC cell types by a noninvasive surgical procedure, we conclude that the ear may prove to be a potential source of autologous cells for regenerative medicine, as supported by the fact that ears are one of the best sources of cells for somatic cell nuclear transfer (SCNT).
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PMID:Ear mesenchymal stem cells (EMSC) can differentiate into spontaneously contracting muscle cells. 1737 Mar 16

We assessed the possible association between variants of the genes encoding for the angiotensin-converting enzyme ( ACE) and alpha-actinin-3 ( ACTN3) (both individually and combined) and several endurance phenotypic traits, e.g., peak power output (PPO), ventilatory (VT) and respiratory compensation threshold (RCT), among others, in professional road cyclists and sedentary controls (n = 46 each). We applied an ANCOVA test using the aforementioned phenotype traits as dependent variables, ACE and/or ACTN3 genotype as the fixed (independent) factor and age and body mass as covariates. We only found a significant genotype effect with no concomitant covariate effect for ACTN3, with cyclists who were not alpha-actinin-3 deficient (RR + RX genotypes) having higher PPO and VT values than their XX counterparts (mean [SEM]: 7.4 (0.1) vs. 7.1 (0.1) W/kg, p = 0.035; and 4.5 (0.1) vs. 4.3 (0.1) W/kg, p = 0.029, respectively). Cyclists with an "extreme" ACTN3 and ACE genotype combination, i.e., most strength/power oriented (DD + RR/RX), had higher RCT values than those with the "intermediate" combinations (II + RX/RR, p = 0.036; and DD + XX, p = .0004) but similar to those with the most endurance oriented genotype (II + XX). No significant differences (p > 0.05) were found in controls. In summary, in world-class cyclists, we only found an association between ACTN3 genotypes and VT and PPO, and between ACTN3/ACE genotype combinations and RCT.
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PMID:Endurance performance: genes or gene combinations? 1865 73

Muscle mass is an important factor influencing the activity of daily living in older adults. We aimed to investigate whether alpha-actinin-3 (ACTN3) gene R577X polymorphism affects muscle mass in older Japanese women. A total of 109 women (mean+/-SD, 64.1+/-6.0 years) were genotyped for the R/X variant of ACTN3. Mid-thigh muscle cross-sectional area (CSA) was assessed using MRI and compared using analysis of covariance models adjusted for body weight. In addition, physical activity and protein intake were measured as the living environmental factors affecting muscle mass. The ACTN3 R577X genotype distributions of the subjects were 19, 63 and 27 for the RR, RX, and XX genotypes, respectively. No differences in physical activity and protein intake were observed among the genotypes. The XX genotype showed lower thigh muscle CSA compared with RR&RX genotype (mean+/-SEM; XX: 69.1+/-1.8 cm(2), RR&RX: 73.6+/-1.1 cm(2); p<0.05). The results of the present study suggest that ACTN3 R577X polymorphism influences muscle mass in older Japanese women.
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PMID:ACTN3 polymorphism affects thigh muscle area. 2022 7