PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 8142011-1 1994 Distinct differences have been described in the development of C3H/He mouse liver tumors induced by the genotoxic carcinogen diethylnitrosamine (DEN) and by the nongenotoxic agent phenobarbitone (PB) in terms of pathology and the frequency of mutation at codon 61 of the Ha-ras oncogene. Diethylnitrosamine 145-148 Harvey rat sarcoma virus oncogene Mus musculus 271-277 8353844-1 1993 In a previous study, the spectrum of H-ras mutations detected in B6C3F1 mouse liver tumors induced by 5, 50 or 150 mumol/kg body wt of N-nitrosodiethylamine (NDEA) was similar to that in spontaneous B6C3F1 mouse liver tumors, suggesting that activation of the H-ras gene in NDEA-induced mouse liver tumors may not be the direct result of the chemical interaction with the H-ras gene. Diethylnitrosamine 135-156 Harvey rat sarcoma virus oncogene Mus musculus 37-42 8353844-3 1993 Twenty-one of 66 NDEA-induced B6C3F1 mouse liver tumors contained activated H-ras gene with 2 of 21 having a CG to AT transversion at the first base of codon 61, 17 of 21 having AT to GC transition and 2 of 21 having an AT to TA transversion at the second base of codon 61 in the H-ras gene. Diethylnitrosamine 17-21 Harvey rat sarcoma virus oncogene Mus musculus 76-81 8353844-3 1993 Twenty-one of 66 NDEA-induced B6C3F1 mouse liver tumors contained activated H-ras gene with 2 of 21 having a CG to AT transversion at the first base of codon 61, 17 of 21 having AT to GC transition and 2 of 21 having an AT to TA transversion at the second base of codon 61 in the H-ras gene. Diethylnitrosamine 17-21 Harvey rat sarcoma virus oncogene Mus musculus 280-285 1638698-0 1992 Temporal changes in the mutant frequency and mutation spectra of the 61st codon of the H-ras oncogene following exposure of B6C3F1 mice to N-nitrosodiethylamine (DEN). Diethylnitrosamine 139-160 Harvey rat sarcoma virus oncogene Mus musculus 87-92 1638698-0 1992 Temporal changes in the mutant frequency and mutation spectra of the 61st codon of the H-ras oncogene following exposure of B6C3F1 mice to N-nitrosodiethylamine (DEN). Diethylnitrosamine 162-165 Harvey rat sarcoma virus oncogene Mus musculus 87-92 1638698-9 1992 These data indicate that DEN-induced mutations at the 61st codon of the mouse H-ras oncogene (i) are an infrequent event, (ii) have different frequencies at the 38 and 65 week timepoints and (iii) are different from the types of mutations seen in spontaneous lesions. Diethylnitrosamine 25-28 Harvey rat sarcoma virus oncogene Mus musculus 78-83 1323970-0 1992 Role of mutations at codon 61 of the c-Ha-ras gene during diethylnitrosamine-induced hepatocarcinogenesis in C3H/He mice. Diethylnitrosamine 58-76 Harvey rat sarcoma virus oncogene Mus musculus 37-45 1747936-0 1991 Analysis of the Ha-ras oncogene in C3H/He mouse liver tumours derived spontaneously or induced with diethylnitrosamine or phenobarbitone. Diethylnitrosamine 100-118 Harvey rat sarcoma virus oncogene Mus musculus 16-22 1747936-1 1991 In a study of the mechanisms involved in the induction of tumours by chemicals, the Ha-ras oncogene was analysed in liver tumours induced by the genotoxic carcinogen diethylnitrosamine (DEN), or the non-genotoxic agent phenobarbitone (PB) in C3H/He mice. Diethylnitrosamine 166-184 Harvey rat sarcoma virus oncogene Mus musculus 84-90 1747936-1 1991 In a study of the mechanisms involved in the induction of tumours by chemicals, the Ha-ras oncogene was analysed in liver tumours induced by the genotoxic carcinogen diethylnitrosamine (DEN), or the non-genotoxic agent phenobarbitone (PB) in C3H/He mice. Diethylnitrosamine 186-189 Harvey rat sarcoma virus oncogene Mus musculus 84-90 1747936-6 1991 Low and variable expression of the Ha-ras gene was detected in all liver tissues with moderately raised levels (175-200%) in spontaneous, DEN and PB-induced tumours as compared to normal liver tissue. Diethylnitrosamine 138-141 Harvey rat sarcoma virus oncogene Mus musculus 35-41 1747936-8 1991 The frequency of the Ha-ras mutation at codon 61 in DEN-induced tumours is greater than in spontaneously arising tumours. Diethylnitrosamine 52-55 Harvey rat sarcoma virus oncogene Mus musculus 21-27 2000226-1 1991 By selective oligonucleotide hybridization of polymerase chain reaction (PCR) amplified tumor DNAs we have analysed the incidence of mutations at codon 61 of the Ha-ras gene in 42 liver tumors spontaneously developed in Balb/c, C3Hf and B6C3 male mice, and in 79 liver tumors induced by the chemical carcinogens diethylnitrosamine (NDEA) and urethan in B6C3 and B6C male and female mice. Diethylnitrosamine 312-330 Harvey rat sarcoma virus oncogene Mus musculus 162-168 2000226-1 1991 By selective oligonucleotide hybridization of polymerase chain reaction (PCR) amplified tumor DNAs we have analysed the incidence of mutations at codon 61 of the Ha-ras gene in 42 liver tumors spontaneously developed in Balb/c, C3Hf and B6C3 male mice, and in 79 liver tumors induced by the chemical carcinogens diethylnitrosamine (NDEA) and urethan in B6C3 and B6C male and female mice. Diethylnitrosamine 332-336 Harvey rat sarcoma virus oncogene Mus musculus 162-168 2000226-4 1991 NDEA-induced tumors showed a low incidence of Ha-ras mutations in both the hybrid mice (3/18 and 1/13 in B6C3 and B6C male mice, respectively). Diethylnitrosamine 0-4 Harvey rat sarcoma virus oncogene Mus musculus 46-52 2000226-6 1991 Our results indicate that liver tumors induced by NDEA or urethan or spontaneously arisen have a different pattern of Ha-ras mutations at codon 61 and that these mutations constitute a rare molecular alteration in the pathogenesis of liver tumors in genetically resistant mice. Diethylnitrosamine 50-54 Harvey rat sarcoma virus oncogene Mus musculus 118-124 2675901-7 1989 Our results demonstrate that approximately 15% of the glucose-6-phosphatase-negative lesions that occurred 24-28 wk after a single injection of diethylnitrosamine contain either C----A transversions at the first base or A----G transitions and A----T transversions at the second base of codon 61 of the Ha-ras gene. Diethylnitrosamine 144-162 Harvey rat sarcoma virus oncogene Mus musculus 302-308 2827904-5 1988 Activating mutations in the H-ras genes from the DEN-induced mouse liver tumors were characterized by selective oligonucleotide hybridization and the detection of a new XbaI restriction site by Southern blot analysis. Diethylnitrosamine 49-52 Harvey rat sarcoma virus oncogene Mus musculus 28-33 2827904-6 1988 In activated H-ras genes from the DEN-induced mouse liver tumor DNA, seven of 14 had a CG----AT transversion at the first base of the 61st codon, three of 14 had an AT----GC transition and four of 14 had the AT----TA transversion at the second base of codon 61. Diethylnitrosamine 34-37 Harvey rat sarcoma virus oncogene Mus musculus 13-18 2827904-8 1988 Taken together, the data suggest that the DEN-induced rat and mouse liver carcinogenesis may involve genetic targets other than or in addition to the H-ras gene. Diethylnitrosamine 42-45 Harvey rat sarcoma virus oncogene Mus musculus 150-155 24535843-1 2014 The process of hepatocarcinogenesis in the diethylnitrosamine (DEN) initiation/phenobarbital (PB) promotion mouse model involves the selective clonal outgrowth of cells harboring oncogene mutations in Ctnnb1, while spontaneous or DEN-only-induced tumors are often Ha-ras- or B-raf-mutated. Diethylnitrosamine 43-61 Harvey rat sarcoma virus oncogene Mus musculus 264-270 24535843-1 2014 The process of hepatocarcinogenesis in the diethylnitrosamine (DEN) initiation/phenobarbital (PB) promotion mouse model involves the selective clonal outgrowth of cells harboring oncogene mutations in Ctnnb1, while spontaneous or DEN-only-induced tumors are often Ha-ras- or B-raf-mutated. Diethylnitrosamine 63-66 Harvey rat sarcoma virus oncogene Mus musculus 264-270 17928010-3 2008 In total, 73% (102/140) of tumors induced by a single application of N-nitrosodiethylamine or 7,12-dimethylbenz[a]anthracene contained either B-raf or Ha-ras mutations and only <3% (4/140) were mutated in both genes. Diethylnitrosamine 69-90 Harvey rat sarcoma virus oncogene Mus musculus 151-157 15592514-4 2005 We now screened 82 N-nitrosodiethylamine-induced liver tumors from C3H/He mice for mutations within the hotspot positions in the Ha-ras and B-raf genes. Diethylnitrosamine 19-40 Harvey rat sarcoma virus oncogene Mus musculus 129-135 11753661-6 2001 In tumors from mice treated with DEN alone, the prevalence of Ha-ras mutations was approximately 30% (6/20), while no beta-catenin mutations (0/13) were detectable in tumors of this treatment group. Diethylnitrosamine 33-36 Harvey rat sarcoma virus oncogene Mus musculus 62-68 11753661-7 2001 By contrast, Ha-ras mutations were undetectable in tumors from mice treated with DEN/PB (0/32), while approximately 80% (37/46) of tumors from this group showed beta-catenin mutations. Diethylnitrosamine 81-84 Harvey rat sarcoma virus oncogene Mus musculus 13-19 25706765-5 2015 Since nitric oxide (NO) participates directly in hippocampal glutamatergic signaling, we investigated the neuronal role of the heme-regulated eukaryotic initiation factor eIF2alpha kinase (HRI), which can bind NO by a heme group, in BACE1 translation and its physiological consequences. Heme 127-131 eukaryotic translation initiation factor 2 alpha kinase 1 Mus musculus 189-192 25706765-5 2015 Since nitric oxide (NO) participates directly in hippocampal glutamatergic signaling, we investigated the neuronal role of the heme-regulated eukaryotic initiation factor eIF2alpha kinase (HRI), which can bind NO by a heme group, in BACE1 translation and its physiological consequences. Heme 127-131 beta-site APP cleaving enzyme 1 Mus musculus 233-238 26042224-2 2015 Neudesin with a conserved cytochrome 5-like heme/steroid-binding domain activates intracellular signaling pathways possibly through the activation of G protein-coupled receptors. Heme 44-48 neuron derived neurotrophic factor Mus musculus 0-8 25874809-6 2015 On the basis of these studies, the most probable mechanism for the inactivation of nNOS involves oxidative demethylation with the resulting thiol coordinating to the cofactor heme iron. Heme 175-179 nitric oxide synthase 1 Homo sapiens 83-87 25874809-7 2015 Although nNOS is a heme-containing enzyme, this is the first example of a NOS that catalyzes an S-demethylation reaction; the novel mechanism of inactivation described here could be applied to the design of inactivators of other heme-dependent enzymes. Heme 19-23 nitric oxide synthase 1 Homo sapiens 9-13 25874809-7 2015 Although nNOS is a heme-containing enzyme, this is the first example of a NOS that catalyzes an S-demethylation reaction; the novel mechanism of inactivation described here could be applied to the design of inactivators of other heme-dependent enzymes. Heme 229-233 nitric oxide synthase 1 Homo sapiens 9-13 25955715-6 2015 The human endogenous protein, alpha1-microglobulin (A1M), removes cell-free heme-groups and induces natural tissue repair mechanisms. Heme 76-80 alpha-1-microglobulin/bikunin precursor Homo sapiens 52-55 25723358-3 2015 Originally designed to mimic the bis-His cytochrome b, the Mimochrome structure was modified to introduce a peroxidase-like activity, by creating a distal cavity on the heme. Heme 169-173 mitochondrially encoded cytochrome b Homo sapiens 41-53 25849895-1 2015 Heme oxygenase (HO) catalyzes a key step in heme homeostasis: the O2- and NADPH-cytochrome P450 reductase-dependent conversion of heme to biliverdin, Fe, and CO through a process in which the heme participates both as a prosthetic group and as a substrate. Heme 44-48 cytochrome p450 oxidoreductase Homo sapiens 74-105 25849895-1 2015 Heme oxygenase (HO) catalyzes a key step in heme homeostasis: the O2- and NADPH-cytochrome P450 reductase-dependent conversion of heme to biliverdin, Fe, and CO through a process in which the heme participates both as a prosthetic group and as a substrate. Heme 130-134 cytochrome p450 oxidoreductase Homo sapiens 74-105 25849895-1 2015 Heme oxygenase (HO) catalyzes a key step in heme homeostasis: the O2- and NADPH-cytochrome P450 reductase-dependent conversion of heme to biliverdin, Fe, and CO through a process in which the heme participates both as a prosthetic group and as a substrate. Heme 130-134 cytochrome p450 oxidoreductase Homo sapiens 74-105 25849895-2 2015 Mammals contain two isoforms of this enzyme, HO2 and HO1, which share the same alpha-helical fold forming the catalytic core and heme binding site, as well as a membrane spanning helix at their C-termini. Heme 129-133 heme oxygenase 2 Homo sapiens 45-48 25849895-2 2015 Mammals contain two isoforms of this enzyme, HO2 and HO1, which share the same alpha-helical fold forming the catalytic core and heme binding site, as well as a membrane spanning helix at their C-termini. Heme 129-133 heme oxygenase 1 Homo sapiens 53-56 25849895-3 2015 However, unlike HO1, HO2 has an additional 30-residue N-terminus as well as two cysteine-proline sequences near the C-terminus that reside in heme regulatory motifs (HRMs). Heme 142-146 heme oxygenase 2 Homo sapiens 21-24 25849895-9 2015 Taken together with EPR measurements, which show the appearance of a new low-spin heme signal in reduced HO2, it appears that a cysteine residue(s) in the HRMs directly interacts with a second bound heme. Heme 82-86 heme oxygenase 2 Homo sapiens 105-108 25849895-9 2015 Taken together with EPR measurements, which show the appearance of a new low-spin heme signal in reduced HO2, it appears that a cysteine residue(s) in the HRMs directly interacts with a second bound heme. Heme 199-203 heme oxygenase 2 Homo sapiens 105-108 25853617-0 2015 The C-terminal heme regulatory motifs of heme oxygenase-2 are redox-regulated heme binding sites. Heme 15-19 heme oxygenase 2 Homo sapiens 41-57 25853617-1 2015 Heme oxygenase-2 (HO2), an enzyme that catalyzes the conversion of heme to biliverdin, contains three heme regulatory motifs (HRMs) centered at Cys127, Cys265, and Cys282. Heme 67-71 heme oxygenase 2 Homo sapiens 0-16 25853617-1 2015 Heme oxygenase-2 (HO2), an enzyme that catalyzes the conversion of heme to biliverdin, contains three heme regulatory motifs (HRMs) centered at Cys127, Cys265, and Cys282. Heme 67-71 heme oxygenase 2 Homo sapiens 18-21 25853617-1 2015 Heme oxygenase-2 (HO2), an enzyme that catalyzes the conversion of heme to biliverdin, contains three heme regulatory motifs (HRMs) centered at Cys127, Cys265, and Cys282. Heme 102-106 heme oxygenase 2 Homo sapiens 0-16 25853617-1 2015 Heme oxygenase-2 (HO2), an enzyme that catalyzes the conversion of heme to biliverdin, contains three heme regulatory motifs (HRMs) centered at Cys127, Cys265, and Cys282. Heme 102-106 heme oxygenase 2 Homo sapiens 18-21 25853617-2 2015 Previous studies using the soluble form of human HO2 spanning residues 1-288 (HO2sol) have shown that a disulfide bond forms between Cys265 and Cys282 and that, in this oxidized state, heme binds to the catalytic site of HO2sol via His45. Heme 185-189 heme oxygenase 2 Homo sapiens 49-52 25853617-2 2015 Previous studies using the soluble form of human HO2 spanning residues 1-288 (HO2sol) have shown that a disulfide bond forms between Cys265 and Cys282 and that, in this oxidized state, heme binds to the catalytic site of HO2sol via His45. Heme 185-189 heme oxygenase 2 Homo sapiens 78-81 25853617-4 2015 In an effort to understand how the HRMs are involved in binding of heme to disulfide-reduced HO2sol, in the work described here, we further investigated the properties of Fe(3+)-heme bound to HO2. Heme 67-71 heme oxygenase 2 Homo sapiens 93-96 25853617-6 2015 We found that HO2tail in the disulfide-reduced state binds Fe(3+)-heme and accounts for the spectral features observed upon binding of heme to the disulfide-reduced form of HO2sol that cannot be attributed to heme binding at the catalytic site. Heme 66-70 heme oxygenase 2 Homo sapiens 14-17 25853617-6 2015 We found that HO2tail in the disulfide-reduced state binds Fe(3+)-heme and accounts for the spectral features observed upon binding of heme to the disulfide-reduced form of HO2sol that cannot be attributed to heme binding at the catalytic site. Heme 135-139 heme oxygenase 2 Homo sapiens 14-17 25891083-7 2015 Mitochondrial membrane potential (DeltaPsim) was detected with JC-1 staining under a fluorescence microscope and quantified by fluorescence ratio detection.Overexpression of appoptosin in SH-SY5Y cells markedly increased cell apoptosis accompanied by reduced HO-1 expression, increased intracellular heme level, ROS overproduction and DeltaPsim impairment. Heme 300-304 solute carrier family 25 member 38 Homo sapiens 174-184 25891083-10 2015 RESULTS: Overexpression of appoptosin in SH-SY5Y cells markedly increased cell apoptosis accompanied by reduced HO-1 expression, increased intracellular heme level, ROS overproduction and DeltaPsim impairment. Heme 153-157 solute carrier family 25 member 38 Homo sapiens 27-37 25891083-13 2015 CONCLUSION: Curcumin inhibits appoptosin-induced apoptosis in SH-SY5Y cells by upregulating the expression of HO-1, reducing the production of intracellular heme and ROS, and preventing the DeltaPsim loss. Heme 157-161 solute carrier family 25 member 38 Homo sapiens 30-40