Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.60 (caspase-7)
 920 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bile salts have been shown to be involved in the etiology of colorectal cancer. Although there is a large body of evidence for bile salts as a cocarcinogen in azoxymethane-induced colorectal cancer, bile salt-induced apoptosis of colorectal cancer cells has not yet been studied in detail. Therefore, we investigated the effects of different bile salts on apoptosis and apoptotic signaling in colon cancer cell lines. Incubation of colorectal cancer cell lines with physiological concentrations of deoxycholic acid led to a dramatic induction of apoptosis. Caspase cleavage and caspase activation occurred as early as 30 min after the addition of deoxycholate. Caspase-2 (Ich-1, Nedd2), caspase-3 (CPP-32, YAMA, Apopain), caspase-7 (Mch-3, ICE-LAP-3), and caspase-8 (FLICE, Mach-1, Mch5) are activated in HT-29, whereas caspase-1 (ICE) remained intact. Caspase activation and cellular apoptosis induced by bile salts were reversed by broad spectrum and selective caspase inhibitors. As opposed to hepatocyte death mediated by bile acids, CD95 was not involved in deoxycholate-induced apoptosis. The cytoprotective effect of ursodeoxycholic acid in hepatocytes or other tumor cell lines, which is mediated by inhibiting the mitochondrial permeability transition, was not observed in colon cancer cell lines as well. This points to distinct intracellular functions of ursodeoxycholate in different cancer cell types. Here we describe the specificity of bile salt-induced apoptosis in colon cancer cell lines. Differences from hepatocytes are shown. Bile acid-specific caspase activation is part of the apoptotic pathway induced by bile salts in colon cancer cell lines. Furthermore, a lack of cytoprotective function of ursodeoxycholate in these cells is demonstrated. Our data raise questions as to the role of bile salts in colorectal carcinogenesis.
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PMID:Characterization of bile salt-induced apoptosis in colon cancer cell lines. 1094 41

Poly (ADP-ribose) polymerase is a zinc-finger DNA-binding enzyme which detects and signals DNA strand breaks generated either directly during base excision repair, or indirectly by genotoxic agents such as oxygen radicals. In response to genotoxic injury, PARP catalyses the synthesis of poly (ADP-ribose), from its substrate beta-NAD+ and this polymer is covalently attached to several nuclear proteins and PARP itself. As a result, PARP converts DNA breaks into intracellular signals which activate DNA repair programs or cell death options. Several studies have also shown that PARP is involved in either necrosis and subsequent inflammation or apoptosis. Although this enzyme is not indispensable during the latter cell death program, it has been demonstrated that PARP plays a facilitating role in this process. PARP is activated at an intermediate stage of apoptosis and is then cleaved and inactivated at a late stage by apoptotic proteases, namely caspase-3/CPP-32/Yama/apopain and caspase-7. This cleavage prevents necrosis during apoptosis, avoiding inflammation. All these functions, and the observation that PARP is an abundant and highly conserved enzyme, suggest that this enzyme plays a pivotal role, particularly in the maintenance of genomic DNA stability, apoptosis and in the response to oxidative stress. Since these situations are found in cancer, inflammation, autoimmunity (such as diabetes), myocardial dysfunction, certain infections, ageing and radiation/chemical exposure, attempts have been made to modulate PARP activity. With regard to the increasing interest towards PARP, the aim of this review is to explain the cellular role of PARP and the advantages of modulating its activity in diverse preventive or therapeutic strategies.
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PMID:Modulating poly (ADP-ribose) polymerase activity: potential for the prevention and therapy of pathogenic situations involving DNA damage and oxidative stress. 1216 82

Alzheimer's disease (AD) is the major cause of dementia, accounting for 50% to 70% of the late-onset patients, with 17 to 20 million affected. It is characterized by neurofibrillary tangles, neuronal loss, and amyloid plaques in tissues of the cortex, hippocampus, and amygdala. Apoptosis or programmed cell death appears in the progression of AD. In this study, we investigated the gene expression of 14 apoptotic genes (E2F1, p21/WAF, ICE-LAP3, Fas Antigen, CPP-32, GADD153, ICE-beta, c-Fos, c-Jun, Bax-alpha, Bcl-2, Bcl-(x)L, BAK, and p53) in 5 normal and 6 AD human hippocampal tissues, using reverse transcription-polymerase chain reaction. Our results show an upregulation of gene expression in AD patients for c-Fos and BAK. ICE-beta, c-Jun, Bax-alpha, Bcl-x(L), p53, and GADD153 were found to be upregulated in some AD samples but were not detected or downregulated in other AD or normal samples. No gene expression was found for E2F1 , p21/WAF, ICE-LAP3, Fas Antigen, CPP32, or Bcl-2. These results indicate significant increases in c-Fos , c-Jun, and Bak; therefore, we suggest that these genes may be critical in the apoptotic cascades of AD.
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PMID:Apoptotic gene expression in Alzheimer's disease hippocampal tissue. 1771 63

Genetic variations in the caspase genes CASP-3 and CASP-7 are known to be involved in apoptosis, cytokine maturation, cell growth and differentiation. Polymorphisms of CASP-3 and CASP-7 genes have been increasingly recognized as important regulators in the development of cancer. However, whether there is a specific association is still controversial. Therefore, we made a Human Genome Epidemiology review and meta-analysis to explore the association between polymorphisms of CASP-3 and CASP-7 genes and cancer risk. Based on the inclusion criteria, we examined 9 case-control studies, with a total of 3142 cancer cases and 3670 healthy controls. Meta-analysis results showed that the homozygote (CC) of rs2705897 in the CASP-3 gene is positively associated with cancer susceptibility [odds ratio (OR) = 4.36, 95% confidence interval (CI) = 1.26-15.11, P = 0.02], while the C allele and C carrier (TC+CC) of rs1049216 are negatively associated with cancer risk (OR = 0.81, 95%CI = 0.69-0.95, P = 0.01; OR = 0.78, 95%CI = 0.63-0.97, P = 0.02, respectively). The G allele and G carrier of rs4647603 (A/G) in CASP-3 had positive associations with cancer susceptibility (OR = 1.69, 95%CI = 1.37-2.09, P < 0.001; OR = 1.93, 95%CI = 1.26-2.93, P = 0.002, respectively). The T allele of rs12415607, the G allele and homozygote (GG) of rs2227310, and homozygote (CC) of rs3124740 also had positive associations with cancer risk (OR = 1.18, 95%CI = 1.02-1.37, P = 0.03; OR = 1.17, 95%CI = 1.01-1.34, P = 0.03; OR = 1.34, 95%CI = 1.04-1.74, P = 0.03; OR = 1.30, 95%CI = 1.04-1.63, P = 0.02, respectively). In addition, homozygote (AA) of rs11196418 showed a significant negative association with cancer risk (OR = 0.36, 95%CI = 0.14-0.93, P = 0.03). These meta-analysis results demonstrated that CASP-3 and CASP-7 genetic polymorphisms are involved in the pathogenesis of cancer.
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PMID:HuGE systematic review and meta-analysis demonstrate association of CASP-3 and CASP-7 genetic polymorphisms with cancer risk. 2376 63


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