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)

Castration of young and old male Brown Norway rats induces apoptosis in the ventral, but not in the dorsal and lateral, lobes of the prostate gland, and apoptosis in old rats is diminished by 50% compared with that in young rats. In this study we examined the lobe-specific and age-dependent expression of Bcl-2 and Bax proteins. Bcl-2 levels in the ventral lobe were 5-fold lower compared with expression in the dorsal and lateral lobes. Bax expression in the ventral lobe was 2- and 20-fold higher than that in the lateral and dorsal lobes, respectively. In all three lobes, Bcl-2 was detected in epithelial cells, but not in stromal cells, whereas Bax protein was localized in both cell types. After castration, Bcl-2 expression in the ventral lobe decreased significantly from the control level after 2-3 d, but increased significantly by 7-10 d. By contrast, Bax expression increased significantly by d 1, gradually decreased by 2-4 d, and was nearly undetectable by 7-10 d postcastration. In the dorsal and lateral lobes, neither Bcl-2 nor Bax expression was significantly altered after castration. In the ventral lobe of old rats after castration, Bcl-2 followed a pattern of expression similar to that observed in young rats. However, Bax levels were 50% lower in old rats compared with those in young rats on d 1 after castration. Therefore, cell death follows the down-regulation of Bcl-2 expression in the ventral lobe of young and old rats. Moreover, the higher relative levels of Bcl-2 expression in the dorsal and lateral lobes of intact animals and in the ventral lobe by 7-10 d after castration serve to protect cells from apoptosis.
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PMID:Bcl-2 protein expression correlates with cell survival and androgen independence in rat prostatic lobes. 1195 65

Inhibitors of differentiation (Id) proteins are repressors of myogenic regulatory factors and have been implicated in apoptosis and muscle atrophy during aging. Indeed, we have previously found that Id levels are elevated in muscles from old rodents, possibly as a consequence of loss of alpha-motoneurons during senescence. To determine if Id2 proteins increase after denervation and if this is accompanied by increased apoptosis in aged as compared with adult animals, the gastrocnemius and soleus muscles were denervated in 1 limb of Fischer 344 x Brown Norway rats aged 9 months (adult, n = 12) and 33 months (aged, n = 9), while the contralateral limb served as the intra-animal control. After 14 days, the muscles in each limb were removed. The levels of Id1, Id2, and Id3 mRNA and protein were significantly greater in muscles of old as compared with young adult rats. Denervation, however, did not significantly increase Id1, Id2, and Id3 mRNA in soleus or gastrocnemius muscles from either young or old rats. Also Id2 protein levels were similar in denervated and control muscles from young adult and old rats. In young adult rats only, denervation induced an increase in Id1 and Id3 protein levels in both the soleus (Id1 113%; Id3 900%) and gastrocnemius (Id1 86%; Id3 80%). Denervation induced a significant increase in caspase 8 in both soleus and gastrocnemius muscles from young (101% and 147%, respectively) and old rats (167% and 190%, respectively). Bax protein levels, as estimated by western blots, increased by 726% and 1087% after denervation in the soleus and by 368% and 49% in the gastrocnemius muscles of young and old rats, respectively. The data suggest that the denervation-induced muscle loss was at least partly due to apoptosis as indicated by elevated caspase 8 and Bax levels in denervated muscles. While Id2 may have a role in aging-induced sarcopenia, Id2 does not appear to directly regulate apoptosis during denervation. The elevated Id expression in muscles from aged animals is therefore not a direct consequence of loss of alpha-motoneurons during senescence.
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PMID:Denervation stimulates apoptosis but not Id2 expression in hindlimb muscles of aged rats. 1290 26

The small G-protein RhoA regulates the actin cytoskeleton, and its involvement in cell proliferation has also been established. In contrast, little is known about whether RhoA participates in cell survival or apoptosis. In cardiomyocytes in vitro, RhoA induces hypertrophic cell growth and gene expression. In vivo, however, RhoA expression leads to development of heart failure (Sah, V. P., Minamisawa, S., Tam, S. P., Wu, T. H., Dorn, G. W., Ross, J. Jr., Chien, K. R., and Brown, J. H. (1999) J. Clin. Investig. 103, 1627-1634), a condition widely associated with cardiomyocyte apoptosis. We demonstrate here that adenoviral overexpression of activated RhoA in cardiomyocytes induces hypertrophy, which transitions over time to apoptosis, as evidenced by caspase activation and nucleosomal DNA fragmentation. The Rho kinase inhibitors Y-27632 and HA-1077 and expression of a dominant negative Rho kinase block these responses. Caspase-9, but not caspase-8, is activated, and its inhibition prevents DNA fragmentation, consistent with involvement of a mitochondrial death pathway. Interestingly, RhoA expression induces a 3-4-fold up-regulation of the proapoptotic Bcl-2 family protein Bax. RhoA also increases levels of activated Bax and the amount of Bax protein localized at mitochondria. Bax mRNA is increased by RhoA, indicating transcriptional regulation, and the ability of a dominant negative p53 mutant to block Bax up-regulation implicates p53 in this response. The involvement of Bax in RhoA-induced apoptosis was examined by treatment with a Bax-inhibitory peptide, which was found to significantly attenuate DNA fragmentation and caspase-9 and -3 activation. The dominant negative p53 also prevents RhoA-induced apoptosis. We conclude that RhoA/Rho kinase activation up-regulates Bax through p53 to induce a mitochondrial death pathway and cardiomyocyte apoptosis.
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PMID:RhoA/Rho kinase up-regulate Bax to activate a mitochondrial death pathway and induce cardiomyocyte apoptosis. 1723 27

Brown rice fermented with Aspergillus oryzae, designated as FBRA, is a dietary fiber-rich food, and fully appreciated as one of the prebiotics, which are generally considered to be beneficial to the health of the body, because of stimulating the growth and/or the activity of bacteria in the digestive system. To assess the effectiveness of FBRA as a functional food, the direct effect of FBRA extract on human colorectal tumor cells was examined. The exposure of HCT116 cells to FBRA extract reduced their viabilities in a concentration-dependent manner, and the reduction of the cell viability might be attributed to the induction of apoptosis probably through the oxidative damage to the cells. Further studies showed that FBRA extract caused a significant elevation of Bax protein and a slight reduction of Bcl2 protein levels, and furthermore caused the activation of caspase-3 in the cells. Thus, it seems reasonable to conclude that FBRA extract can exert oxidative damage to the cells, resulting in apoptotic cell death by activating the mitochondrial pathway in human colorectal tumor cells. Therefore, daily intake of FBRA can be expected to be beneficial for preventing carcinogenesis and/or suppressing tumor growth in the digestive tract.
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PMID:Extract of fermented brown rice induces apoptosis of human colorectal tumor cells by activating mitochondrial pathway. 2238 98