Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunostaining of Bcl-2 protein which represses apoptosis was performed on 178 biopsied human pathologic muscles and 10 control muscles by the ABC method using two monoclonal anti-Bcl-2 antibodies. Bcl-2 in control muscles was positive mainly in nuclear membrane and cytoplasm in type 2 fibers (especially type 2B fibers), and negative in type 1 fibers. In myopathies, it was not expressed in type 2C (regenerating) fibers, and its expression in atrophic fibers such as forming pyknotic nuclear clumps was strong. In inflammatory myopathies, expression was observed in infiltrating lymphocytes, and especially in dermatomyositis in atrophic fibers facing perimysium. In mitochondrial myopathies, the positivity was observed only in type 2 ragged-red fibers. In muscles of neurogenic disorders, both small angulated fibers and atrophic grouped fibers were strongly positive. Western blot analysis using anti-Bcl-2 antibody showed a single band at 26 kDa in control and diseased skeletal muscles. Compared to immunostaining of Fas antigen in serial sections, both Bcl-2 and Fas were expressed in same atrophic fibers in distal myopathy with rimmed vacuoles. In myotonic dystrophy, they were often expressed in type 2 fibers containing internal nucleus. In carriers of Duchenne dystrophy, Fas-positive but Bcl-2 negative fibers were observed in same dystrophin-negative fibers. In conclusion, expression of Bcl-2 in skeletal muscles might suggest that Bcl-2 plays a role on surviving muscle fibers.
 ...
PMID:[Immunostaining of anti-Bcl-2 antibody in diseased human muscles]. 893 93

Expression of the apoptosis-related proteins Bcl-2 and Bax was analysed by means of immunohistochemistry in muscle biopsies from 13 patients suffering from different muscular diseases (inclusion body myositis n=4, polymyositis n=3, Becker muscular dystrophy n=4, necrotizing myopathy n=2, and controls n=4), in an attempt to learn about the role of these proteins in human muscle diseases associated with muscle fiber necrosis and regeneration. Increased Bcl-2 and Bax immunoreactivity was observed as fine granular precipitates in the cytoplasm or as subsarcolemmal aggregates in pathological cases. Increased Bcl-2 and Bax immunoreactivity was detected in some necrotic fibers, regenerating fibers, ring fibers and some apparently normal muscle fibers. In addition, increased Bcl-2 and Bax immunoreactivity was observed in the periphery of rimmed vacuoles and in muscle fibers with abnormal mitochondria in patients suffering from inclusion body myositis. Double-labelling immunohistochemistry disclosed co-localization of both proteins in about 50% of Bcl-2-immunoreactive fibers. Finally, double-labelling immunohistochemistry using N-CAM antibodies revealed that some Bax-positive fibers were regenerating fibers. Since increased Bax immunoreactivity was not restricted to necrotic muscle fibers, the present results suggest that over-expression of this protein in human myopathies is probably independent of the process of cell death.
 ...
PMID:Bcl-2 and Bax protein expression in human myopathies. 1038 52

Congestive heart failure is characterized by a skeletal muscle myopathy with muscle bulk loss. The mechanisms responsible for these changes are not clear at present. We have investigated the role of apoptosis in the rat "slow" soleus muscle during the development of heart failure, which was induced by injection of monocrotaline (30 mg/kg). We looked at the time course of apoptosis by studying six animals at each of the following time points: 0, 17, 24, and 30 days. We found a decreased expression of the antiapoptotic protein Bcl-2, which was accompanied by a rise of proapoptotic caspase-3. Ubiquitin levels did not change. DNA nick-end labeling showed an increased number of apoptotic nuclei both in myofibers and interstitial cells when heart failure occurred. At variance with previous observations in the fast-twitch tibialis anterior muscle in the same animals, in which tumor necrosis factor-alpha (TNF-alpha) increased at the time that apoptosis occurred, the magnitude of apoptosis is lower in soleus muscle and there is no appearance of muscle atrophy. In soleus muscle, apoptosis is accompanied by activation of the caspase-3 system. There is no activation of the TNF-alpha- and ubiquitin-dependent protein waste. In conclusion, slow muscles are less prone to develop apoptosis than fast muscles. Muscle atrophy appears earlier in these latter ones.
 ...
PMID:Apoptosis and atrophy in rat slow skeletal muscles in chronic heart failure. 1056 91

DNA fragmentation and apoptosis-related proteins have been investigated in thyroid cells and there is evidence that Fas-mediated apoptosis is inhibited by thyroid stimulating hormone (TSH). We investigated DNA fragmentation by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and Bcl-2 and Fas antigen expression by immunocytochemistry in skeletal muscles from 12 patients with hypothyroid myopathy and 5 patients with hyperthyroid myopathy. The finding of very few TUNEL-positive muscle fibers in both conditions suggests that apoptosis does not play a role in the pathogenesis of thyroid myopathies. Bcl-2 expression increased significantly in hypothyroid myopathy, correlating with high serum TSH levels, and not with either triiodothyronine (T3) or thyroxine (T4) serum levels. By contrast, Fas antigen was overexpressed in hyperthyroid myopathy, correlating with low TSH levels. These findings suggest an anti-apoptotic role for TSH itself in skeletal muscle.
 ...
PMID:Apoptosis and apoptosis-related proteins in thyroid myopathies. 1221 Mar 68

Skeletal muscle atrophy is a common feature in alcoholism that affects up to two-thirds of alcohol misusers, and women appear to be particularly susceptible. There is also some evidence to suggest that malnutrition exacerbates the effects of alcohol on muscle. However, the mechanisms responsible for the myopathy remain elusive, and some studies suggest that acetaldehyde, rather than alcohol, is the principal pathogenic perturbant. Previous reports on rats dosed acutely with ethanol (<24 h) have suggested that increased proto-oncogene expression (i.e., c-myc) may be a causative process, possibly via activating preapoptotic or transcriptional pathways. We hypothesized that 1) increases in c-myc mRNA levels also occur in muscle exposed chronically to alcohol, 2) muscle of female rats is more sensitive than that from male rats, 3) raising acetaldehyde will also increase c-myc, 4) prior starvation will cause further increases in c-myc mRNA expression in response to ethanol, and 5) other genes involved in apoptosis (i.e., p53 and Bcl-2) would also be affected by alcohol. To test this, we measured c-myc mRNA levels in skeletal muscle of rats dosed either chronically (6-7 wk; ethanol as 35% of total dietary energy) or acutely (2.5 h; ethanol as 75 mmol/kg body wt ip) with ethanol. All experiments were carried out in male Wistar rats (approximately 0.1-0.15 kg body wt) except the study that examined gender susceptibility in male and female rats. At the end of the studies, rats were killed, and c-myc, p53, and Bcl-2 mRNA was analyzed in skeletal muscle by RT-PCR with an endogenous internal standard, GAPDH. The results showed that 1) in male rats fed ethanol chronically, there were no increases in c-myc mRNA; 2) increases, however, occurred in c-myc mRNA in muscle from female rats fed ethanol chronically; 3) raising endogenous acetaldehyde with cyanamide increased c-myc mRNA in acute studies; 4) starvation per se increased c-myc mRNA levels and at 1 day potentiated the acute effects of ethanol, indicative of a sensitization response; 5) the only effect seen with p53 mRNA levels was a decrease in muscle of rats starved for 1 day compared with fed rats, and there was no statistically significant effect on Bcl-2 mRNA in any of the experimental conditions. The increases in c-myc may well represent a preapoptotic effect, or even a nonspecific cellular stress response to alcohol and/or acetaldehyde. These data are important in our understanding of a common muscle pathology induced by alcohol.
 ...
PMID:Acute and chronic effects of alcohol exposure on skeletal muscle c-myc, p53, and Bcl-2 mRNA expression. 1287 71

A time course study was performed to reveal the sequence of histopathology after Trichinella spiralis or T. pseudospiralis infection in mice. A cyst was formed in the former case by about 18 days post infection and prominent myopathy was restricted within the cyst. In the latter case, however, no typical cyst was formed, and myopathy spread diffusely over the infected muscle tissues occupying half the area of muscle sections. An electron microscope observation revealed that the disintegration of muscle cells was delayed in T. pseudospiralis infection than in T. spiralis infection. Quantitative reverse transcription polymerase chain reaction (RT-PCR) showed that apoptosis-related genes were expressed for a longer term in muscles infected with T. pseudospiralis than in those with T. spiralis, although the same spectrum of genes are mobilized. Examined apoptosis-related genes included tumor suppressor genes p53, p53; mouse double minute 2, MDM2; cyclin-dependent kinase inhibitor p21 (WAF1), p21(waf) ; Bcl-2 associated protein X, BAX; apoptotic protease activating factor 1, Apaf-1; Caspase 9 and serine/ threonine protein kinase, PKB. Micro-dissection of the infected muscle tissue and subsequent RT-PCR confirmed that the expressions of these genes are restricted to tissue with myopathy. Thus, the expression of the apoptosis-related genes correlated with continuous and diffuse myopathy caused by T. pseudospiralis infection.
 ...
PMID:Trichinella pseudospiralis infection is characterized by more continuous and diffuse myopathy than T. spiralis infection. 1594 11

Apoptotic cell death of differentiated skeletal muscle has been reported in an experimental steroid-induced myopathy of rats. To investigate the underlying molecular changes in the apoptosis of skeletal muscle, in situ end labeling (ISEL), Fas expression, and Western blot analysis for apoptosis-related proteins in the soleus muscle of triamcinolone acetonide (TA)-induced myopathy of rats were studied. Proteins for Western blot analysis included Fas-associated death domain (FADD) and caspase 8 for extrinsic pathway, as well as Bcl-2, Bcl-XL, Bax, Bad, Bid, Akt, p-Akt, and caspase 9 for intrinsic pathway. ISEL-positive myonuclei in TA-treated rats were 1.8 +/- 1.2%, whereas Fas-positive muscle fibers were 4.5 +/- 2.0%. One-fourth of Fas-positive muscle fibers had ISEL-positive myonuclei. Levels of FADD, Bax, Bad, and Bid were substantially increased in the TA-induced myopathy group, whereas Bcl-2, Bcl-XL, Akt, p-Akt, and caspase 9 did not change between control and myopathy groups. Caspase 8 activity increased in the myopathy group. These findings indicate that apoptosis of skeletal muscle in TA-induced myopathy may be triggered by Fas-Fas ligand signals and promoted mainly by overexpression of the pro-apoptotic molecules of FADD and caspase 8 involving the extrinsic pathway. The apoptotic process presented in this study supports a direct, nongenomic effect of a glucocorticoid on cellular membranes leading to cellular apoptosis rather than genomic effector mechanism of steroid hormone mediated by cytosolic steroid receptors.
 ...
PMID:Apoptosis of skeletal muscle on steroid-induced myopathy in rats. 1598 69

To identify the diagnostic pitfalls as well as the value of immunohistochemical studies in making a pathologic evaluation of a pediatric intestinal pseudo-obstruction (IPO), this study reassessed the pathology of 87 surgically resected intestines from 80 patients under the impression of IPO and 10 normal controls using immunohistochemical studies. The main diagnostic pitfall was the interpretation of the enteric nervous plexuses in the transitional zone and the detection of the indistinct or immature neurons indistinguishable from enteric glial cells or satellite cells. Immunohistochemical study was a very helpful diagnostic adjunct to delineating the immature neurons (bcl2), the size of the enteric ganglia and neuromuscular innervation (S-100 protein, synaptophysin, and CD56), and the interstitial cell of Cajal (c-Kit) and myopathy (SMA). With help of immunohistochemistry, our series of IPO could classify as neuropathy (92.5%), myopathy (2.5%), and the idiopathic forms (3.8%) more clearly. In terms of the types of neuropathy, Hirschsprung's disease (HD), pure hypoganglionosis, and intestinal neuronal dysplasia (IND-B) were diagnosed in 71.3%, 6.3%, and 48.8% of patients, respectively. IND-B was associated with other neuropathies, HD in 77.0% and hypoganglionosis in 7.7%, rather than being present in a pure form. Immature ganglion cells were found in 48.8%. Because a reduced number of interstitial cells of Cajal was commonly associated with HD in 84.2%, hypoganglionosis in 40%, and IND-B in 76.9% of cases, it might be a preceding or aggravating factor related to an IPO. In terms of detecting immature ganglion cells, we found bcl2 most helpful.
 ...
PMID:Immunohistochemical studies of pediatric intestinal pseudo-obstruction: bcl2, a valuable biomarker to detect immature enteric ganglion cells. 1686 87

Germanium (Ge) is commonly used in the semiconductor industry as well as health-promoting and medical field. Biologically, germanium possesses erythropoietic, anti-microbial, anti-tumor, anti-amyloidosis, and immunomodulative effects. However, toxic effects of Ge-containing compounds on kidney, muscle, neuronal cells, and nerves have been reported. Mitochondrial dysfunction was found to be involved in the pathogenesis of GeO(2)-induced nephropathy and myopathy. Since it is well known that mitochondria play a major role in apoptosis triggered by many stimuli, an effort was made to examine whether the Ge-induced neurotoxicity occurs through mitochondria-mediated apoptosis. A mouse neuroblastoma cell line, Neuro-2A, was used in the present study. After incubating with 0.1-800microM of GeO(2) for 0-72h, the cell viability of Neuro-2A cells was inhibited in a dose- and time-dependent manner. Further analysis showed that aside from the changes in the nuclear morphology responsible for apoptosis, the release of cytochrome c, the loss of mitochondrial membrane potential, the translocation of Bax, and the reduction of Bcl-2 expression were also observed in Neuro-2A cells after GeO(2) treatment. These results indicate that the mitochondria-mediated apoptosis is involved in this in vitro model of GeO(2)-induced neurotoxicity.
 ...
PMID:Germanium dioxide induces mitochondria-mediated apoptosis in Neuro-2A cells. 1681 49

Accumulation of protein aggregates is a hallmark of several neurodegenerative disorders as well as for a number of protein conformation-based diseases, including those affecting muscle, liver and heart. Desminopathy or desmin-related myopathy (DRM) is a skeletal myopathy characterized by bilateral muscle weakness, but is often accompanied by cardiomyopathy as well. DRM can be caused by mutations in desmin, alphaB crystallin, myotilin, Z-band alternatively spliced PDZ-containing protein (ZASP), filamin C (FLNC) or Bcl-2-associated athanogene-3 (BAG3). The common pathological pattern in DRM is accumulation of misfolded proteins, however, clinical manifestations can differ significantly.
 ...
PMID:Autophagy in desmin-related cardiomyopathy: thoughts at the halfway point. 2052 25


1 2 3 Next >>