Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enhancing the clearance of neutrophils by enhancing apoptotic cell death and macrophage recognition may be beneficial in acute lung injury. Exogenous nitric oxide gas depresses neutrophil oxidative functions and accelerates cell death (A. H. Daher, J. D. Fortenberry, M. L. Owens, and L. A. Brown. Am. J. Respir. Cell Mol. Biol. 16: 407-412, 1997). We hypothesized that S-nitrosoglutathione (GSNO), a physiologically relevant nitric oxide donor, could also enhance neutrophil DNA fragmentation. Neutrophils were incubated for 2-24 h in the absence and presence of GSNO (dose range 0.1-5 mM) and evaluated for cell death by a fluorescent viability/cytotoxicity assay. Neutrophil DNA fragmentation was assessed by cell death detection ELISA and by terminal deoxynucleotidyltransferase-mediated fluorescence-labeled dUTP nick end labeling assay. Neutrophil oxidative function was also determined. Incubation with GSNO increased cell death at 2, 4, and 24 h. GSNO incubation for 24 h significantly increased DNA fragmentation in a dose-dependent fashion at 0.5 (median 126% of control value; P = 0.002) and 5 mM (185% of control value; P = 0.002) by terminal deoxynucleotidyltransferase-mediated fluorescence-labeled dUTP nick end labeling and at 0.5 mM by ELISA (164% of control value; P = 0.03). The apoptosis-to-total cell death ratio increased with increasing GSNO concentration (P < 0.05). Effects were mitigated by coincubation with superoxide dismutase. Five millimolar GSNO decreased overall superoxide generation and O2 consumption but not when adjusted for dead neutrophils. GSNO significantly enhances cell death and neutrophil DNA fragmentation in a dose-dependent fashion.
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PMID:S-nitrosoglutathione enhances neutrophil DNA fragmentation and cell death. 1007 Jan 7

Growth and differentiation of the prostate gland depends upon androgens, yet overgrowth of the human prostate occurs later in life when serum levels of testosterone are declining. We have reported a similar phenomenon in the Brown Norway rat, but the age-dependent overgrowth of the prostate is confined to the dorsal and lateral lobes and, hence, is lobe specific. Because tissue growth depends upon the balance between proliferation and death of cells, the present study was designed to investigate whether cell death differed in the various prostatic lobes of Brown Norway rats as a function of age. Apoptosis of cells in the ventral, dorsal, lateral, and anterior lobes of the prostate was examined in young (4-month-old) and old (24-month-old) Brown Norway rats after castration. Whereas castration caused tissue weights of all four prostatic lobes to decrease over the course of 10 days, this occurred more rapidly and to a greater magnitude in the ventral than in the dorsal, lateral, and anterior lobes. Tissue DNA content, a measure of cell number, decreased only in the ventral lobe after castration. DNA fragmentation, indicative of apoptotic cell death, was detected by in situ labeling using the terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling method and as intranucleosomal cleavage of genomic DNA analyzed by agarose gel electrophoresis. Both methods demonstrated the correlation between loss of DNA content and apoptotic cell death in the ventral lobe, whereas only the highly sensitive terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) method revealed relatively few dying cells in the dorsal, lateral, and anterior lobes after castration. Moreover, when examined as a function of age, less cell death occurred in all four lobes of old rats compared with young rats. In both young and old rat prostates, cell death was observed in epithelial and stromal cells within the ventral lobe where apoptotic cells were detected throughout the branched ductal network and were not restricted to a particular region. Taken together, these studies demonstrate the marked differences in cell death and survival between the different rat prostatic lobes in response to castration and further suggest that the androgen-sensitive apoptotic response is age dependent. Hence, the lower rates of cell death observed for the dorsal and lateral lobes, accompanied by the further decline that occurs with increasing age, are important components of the age-dependent and lobe-specific overgrowth observed for these lobes. Moreover, the age-dependent decline in apoptotic cell death observed in the prostates of old rats suggests that prostatic cells develop androgen independence as a function of age, and survival of these cells does not require androgen.
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PMID:Castration-induced apoptotic cell death in the Brown Norway rat prostate decreases as a function of age. 1065 Sep 65

Muscle atrophy is associated with a loss of muscle fiber nuclei, most likely through apoptosis. We investigated age-related differences in the extent of apoptosis in soleus muscle of young (6 mo) and old (32 mo) male Fischer 344 x Brown Norway rats subjected to acute disuse atrophy induced by 14 days of hindlimb suspension (HS). HS-induced atrophy (reduction in muscle weight and cross-sectional area) was associated with loss of myofiber nuclei in soleus muscle of young, but not old, rats. This resulted in a significant decrease in the myonuclear domain (cross-sectional area per nucleus) in young and old rats, with changes being more pronounced in old animals. Levels of apoptosis (TdT-mediated dUTP nick end labeling and DNA fragmentation) were higher in soleus muscles of old control rats than young animals. Levels were significantly increased with HS in young and old rats, with the greatest changes in old animals. Caspase-3 activity in soleus muscle tended to be increased with age, but changes were not statistically significant (P=0.052). However, with HS, caspase-3 activity significantly increased in young, but not old, rats. Immunohistochemistry showed that the proapoptotic endonuclease G (EndoG, a mitochondrion-specific nuclease) was localized in the subsarcolemmal mitochondria in control muscles, and translocation to the nucleus occurred in old, but not young, control animals. There was no difference between EndoG total protein content in young and old control rats, but EndoG increased almost fivefold in soleus muscle of old, but not young, rats after HS. These results show that deregulation of myonuclear number occurs in old skeletal muscle and that the pathways involved in apoptosis are distinct in young and old muscles. Apoptosis in skeletal muscle is partly mediated by the subsarcolemmal mitochondria through EndoG translocation to the nucleus in response to HS.
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PMID:Age-related differences in apoptosis with disuse atrophy in soleus muscle. 1565 Jan 25

Despite advances in treatment, age-related cardiac dysfunction still remains a leading cause of cardiovascular death. Recent data have suggested that increases in cardiomyocyte apoptosis may be involved in the pathological remodeling of heart. Here, we examine the effects of aging on cardiomyocyte apoptosis in 6-, 30-, and 36-month-old Fischer344 x Brown Norway F1 hybrid rats (F344XBN). Compared with 6-month hearts, aged hearts exhibited increased TdT-mediated dUTP nick end labeling-positive nuclei, caspase-3 activation, caspase-dependent cleavage of alpha-fodrin and diminished phosphorylation of protein kinase B/Akt (Thr 308). These age-dependent increases in cardiomyocyte apoptosis were associated with alterations in the composition of the cardiac dystrophin glycoprotein complex and elevated cytoplasmic IgG and albumin immunoreactivity. Immunohistochemical analysis confirmed these data and demonstrated qualitative differences in localization of dystrophin-glycoprotein complex (DGC) molecules with aging. Taken together, these data suggest that aging-related increases in cardiac apoptotic activity model may be due, at least in part, to age-associated changes in DGC structure.
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PMID:Possible molecular mechanisms underlying age-related cardiomyocyte apoptosis in the F344XBN rat heart. 2005 83