Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 tumor-suppressor gene is the most commonly altered gene in human cancers. Here we demonstrate that transcripts of the mdm2 gene, which encodes a cellular p53 binding protein, markedly increased in the rat liver within 1 to 3 h, reached a peak at 12 h and returned to the basal level 48 h after the administration of carbon tetrachloride. However, the level of hepatic mdm2 mRNA did not significantly change after partial hepatectomy. This is in contrast to p53 gene expression which increased after either procedure. C-myc transcripts also rapidly increased after the injection of carbon tetrachloride, reaching a maximal level at 3 h. The activity of serum alanine aminotransferase was low within the first 12 h and was maximal 24 h after carbon tetrachloride. These results suggest that the transient hepatic expression of the mdm2 gene prior to the onset of cell death is more likely to reflect events associated with necrosis rather than with cell proliferation.
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PMID:Expression of the protooncogene mdm2 markedly increases in response to carbon tetrachloride but not after partial hepatectomy in contrast to p53. 766 43

We followed 145 men with chronic hepatitis B virus (HBV) hepatitis for 10 years to determine whether exposure to aflatoxin, or concomitant exposure to hepatitis C virus (HCV), or family history of hepatocellular carcinoma (HCC) increased the risk of developing HCC. We collected 8 monthly urine samples before beginning follow-up and pooled them to detect aflatoxin metabolite M1 (AFM1). AFM1 was detected in 78 (54%) of the subjects. The risk of HCC was increased 3.3-fold (with a 95% confidence interval of 1.2-8.7) in those with detectable AFM1 (above 3.6 ng/L). This relative risk was adjusted for age and for HCV status. The attributable risk from exposure to detectable AFM1 was 0.553 (0.087, 0.94). The relative risk of fatal cirrhosis for those with elevated AFM1 was 2.8 (0.6, 14.3), and the odds of having a persistently elevated alanine transaminase (ALT) were 2.5-fold greater in those with detectable AFM1 (P =.007). Concomitant infection with HCV increased the risk of HCC 5.8-fold (2. 0-17), adjusted for age and AFM1 status. A family history of HCC increased the risk of HCC 5.6-fold, adjusted for age and AFM1. Four men with detectable AFM1 and HCC all had missense mutation in codon 249 of the p53 gene in cancer tissues. This study shows that exposure to AFM1 can account for a substantial part of the risk of HCC in men with chronic HBV hepatitis and adds importantly to the evidence that HCV and family history of HCC increase the risk of HCC in men with chronic HBV hepatitis.
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PMID:Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1. 1042 71

Glutathione depletion either decreased or increased death-receptor-mediated apoptosis in previous studies. Comparison of the durations of glutathione depletion before death-receptor stimulation in these studies might suggest a different effect of prolonged versus acute thiol depletion. We compared the effects of the prolonged glutathione depletion caused by a sulfur amino acid-deficient (SAA(-)) diet and the acute depletion caused by a single dose of phorone on hepatic apoptosis triggered by the administration of an agonistic anti-Fas antibody. The chronic SAA(-) diet did not affect hepatic Fas or Bcl-XL, but increased p53 and Bax, and exacerbated Fas-mediated mitochondrial membrane depolarization, electron-microscopy-proven outer mitochondrial membrane rupture, cytochrome c translocation to the cytosol, and caspase 3 activation. These effects were prevented by cyclosporin A, an inhibitor of mitochondrial permeability transition. The SAA(-) diet increased internucleosomal DNA fragmentation, the percentage of apoptotic hepatocytes, serum alanine transaminase (ALT) activity, and mortality after Fas stimulation. Despite a similar decrease in hepatic glutathione, administration of a single dose of phorone 1 hour before the anti-Fas antibody did not change p53 or Bax, and did not enhance Fas-induced mitochondrial permeability transition and toxicity. However, 4 repeated doses of phorone (causing more prolonged glutathione depletion) increased Bax and Fas-mediated toxicity. In conclusion, a chronic SAA(-) diet, but not acute phorone administration, increases p53 and Bax, and enhances Fas-induced mitochondrial permeability transition and apoptosis. Thiol depletion could cause oxidative stress that requires several hours to increase p53; the latter induces Bax, which translocates to mitochondria after Fas stimulation.
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PMID:Prolonged, but not acute, glutathione depletion promotes Fas-mediated mitochondrial permeability transition and apoptosis in mice. 1134 47

Acetaminophen (AAP), the analgesic hepatotoxicant, is a powerful inducer of oxidative stress, DNA fragmentation, and apoptosis. The anti-apoptotic oncogene bcl-XL, and the pro-apoptotic oncogene p53 are two key regulators of cell cycle progression and/or apoptosis subsequent to DNA damage in vitro and in vivo. This study investigated the effect of AAP on the expression of these oncogenes and whether agents that modulate DNA fragmentation (chlorpromazine, CPZ) and DNA repair through poly(ADP-Ribose) polymerase (PARP) activity (4-AB: 4-aminobenzamide) can protect against AAP-induced hepatotoxicity by inhibiting oxidative stress, DNA fragmentation, and/or by altering the expression of bcl-XL and p53. In addition, the protective effect of supplemental nicotinamide (NICO), known to be depleted in cells with high PARP activity during DNA repair, is similarly evaluated. Male ICR mice (3 months old) were administered vehicle alone; nontoxic doses of 4-AB (400 mg/kg, ip), NICO (250 mg/kg, ip) or CPZ (25 mg/kg, ip), hepatotoxic dose of AAP alone (500 mg/kg, ip), or AAP plus one of the protective agents 1 h later. All animals were sacrificed 24 h following AAP administration. Serum alanine aminotransferase activity (ALT), hepatic histopathology and lipid peroxidation, DNA damage, and expression of bcl-XL and p53 (western blot analysis) were compared in various groups. All of the three agents significantly prevented AAP-induced liver injury, lipid peroxidation, DNA damage, and associated apoptotic and necrotic cell deaths, 4-AB being the most effective and NICO the least. Compared to control, there was a considerable decrease in bcl-XL expression, and an increase in p53 expression in AAP-exposed livers. The effect of AAP on bcl-XL was antagonized and that on p53 was synergized by the PARP-modulator 4-AB as well as NICO, whereas the endonuclease inhibitor CPZ was without effect on either bcl-XL or p53 expression. These results suggest that the hepatotoxic effect of AAP involves multiple mechanisms including oxidative stress, upregulation of endonuclease (or caspase-activated DNAse) and alteration of pro- and anti-apoptotic oncogenes. The observed antagonism of AAP-induced hepatocellular apoptosis and/or necrosis by modulators of multiple processes including DNA repair suggests the likelihood that a more effective therapy against AAP intoxication should involve a combination of antidotes.
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PMID:Ca(2+)-calmodulin antagonist chlorpromazine and poly(ADP-ribose) polymerase modulators 4-aminobenzamide and nicotinamide influence hepatic expression of BCL-XL and P53 and protect against acetaminophen-induced programmed and unprogrammed cell death in mice. 1146 65

This is, to our knowledge, the first report of papillary adenocarcinoma originating in the subvesical bile duct. A 77-year-old man was referred to our hospital for further evaluation of liver dysfunction. Serum liver function test results on admission included: aspartate aminotransferase, 99 IU/l; alanine aminotransferase, 149 IU/l; lactate dehydrogenase, 438 IU/l; alkaline phosphatase, 992 IU/l; leucine aminopeptidase, 320 IU/l; and gamma-glutamyl transpeptidase, 593 IU/l. Serum carbohydrate antigen (CA) 19-9 value was high (80 U/ml). Abdominal ultrasonogram, computed tomographic scan, and percutaneous transhepatic cholangiogram demonstrated a mass in the common hepatic duct, and dilatation of the intrahepatic bile ducts. A laparotomy was performed on May 14, 1997. The tumor originated in the dilated subvesical duct that joined the common hepatic duct, and projected into the common hepatic duct. The patient underwent cholecystectomy, resection of the subvesical duct and the common hepatic duct, dissection of regional pericholedochal lymph nodes, and Roux-en-Y hepaticojejunostomy. The resected tumor presented macroscopically as a papillary mass measuring 4.0 x 2.0 cm. The pathological diagnosis was papillary adenocarcinoma. The immunostaining positivity rates for MIB-1 and p53 protein were 49.6% and 33.8%, respectively.
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PMID:Papillary adenocarcinoma of the subvesical duct. 1170 63

There are continuing concerns over the safety of the nation's and the world's blood supply. The allogeneic blood supply is tested for antibodies to HIV1/2, HTLVI/II, hepatitis B, hepatitis C (HCV) and syphilis. Testing is also performed for donor ALT (SGOT) levels, for the presence of hepatitis B surface antigen, human immunodeficiency virus (HIV) p24 antigen and, using nucleic acid amplification testing (NAT), for HIV and HCV nucleic acids. Still, there are concerns regarding other pathogenic agents. Dr. Roger Dodd addresses a series of pathogens that are already known to be transmissible by transfusion. These include malaria, Chagas' disease, babesiosis, bacteria and some viral agents. The need for new donor screening assays to protect the integrity and purity of the blood supply must be balanced against the loss of potential donors and the cost of developing and implementing these new screening assays. This issue will be highlighted. Dr. Edward Snyder reviews the status of research into development of systems for pathogen inactivation (PI) of blood and its components. A proactive technology wherein PI reagents such as psoralen, riboflavin, dimethylmethylene blue or inactine are added to blood collection bags could assure multiple log reduction of a variety of pathogens including viruses, bacteria, protozoa and fungi without the need to initially pre-screen the blood for a specific pathogen. Such a program could also cover new pathogens as they enter the blood supply. As a key issue relates to the toxicology of these agents, Dr. Snyder provides data on a novel carcinogenicity assay that uses a heterozygous p53 knock-out mouse model. The criteria likely to be needed for PI technology to be adopted by the transfusion community are summarized.
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PMID:Reducing the risk of blood transfusion. 1172 97

Telomerase activation and p53 dysfunction are important events in the development and progression of most cancers including ovarian cancer. However, many cancer cell lines and human tumors have been shown to lack telomerase, and maintain telomerase through the ALT (alternative lengthening of telomeres). It is not known whether specific types of p53 mutations are correlated with telomerase activity in human tumors. Invasive ovarian cancers (109) were analyzed for telomerase by ELISA and its subunits human telomerase RNA (hTR), and human telomerase reverse transcriptase (hTERT) by RT-PCR. p53 protein was analyzed in the same samples using immunohistochemistry, and p53 exons 2-11 were analyzed using SSCP and sequence analysis. Telomerase activity was detected in 80 (74%) of 109 tumors. The subunit hTR was consistently present in all ovarian cancer samples, and hTERT was expressed in 96 (88%) tumors. Thirteen (16%) tumors were negative for hTERT and none of these expressed telomerase. Fifty-seven (52%) tumors stained positive for p53, and there was no correlation with telomerase activity based on p53 staining (p = 0.08). Eighty-two (75%) tumors were found to have a p53 mutation, and 40 (36%) tumors contained a null mutation. Only 14% of the tumors with wild type or missense p53 were negative for telomerase activity. In contrast, 19 (48%) of 40 tumors with a p53 null mutation were negative for telomerase activity (p <0.001). There was no difference in the incidence of telomerase positivity between critical site versus non-critical site missense p53 mutations. Seventy-five percent of the tumors with a p53 mutation in the central region were telomerase positive. In contrast, only 47% of the tumors with a mutation in either the amino- or carboxy-terminus were telomerase positive (p = 0.03). Ovarian cancers with a p53 null mutation are more likely to lack telomerase activity. This may have implications for therapeutic approaches based on telomerase.
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PMID:p53 null mutations are associated with a telomerase negative phenotype in ovarian carcinoma. 1249 80

Pyridine is used as a denaturant in alcohol and anti freeze mixtures, as a solvent for paint, rubber, and polycarbonate resins, and as an intermediate in the manufacture of insecticides, herbicides, and fungicides. It is used in the production of piperidine, an intermediate in the manufacture of rubber and mepiquat chloride, and as an intermediate and solvent in the preparation of vitamins and drugs, dyes, textile water repellants, and flavoring agents in food. Pyridine was nominated for study because of its large production volume and its use in a variety of food, medical, and industrial products. Male and female F344/N rats, male Wistar rats, and male and female B6C3F1 mice were exposed to pyridine (approximately 99% pure) in drinking water for 13 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, Drosophila melanogaster, and mouse bone marrow cells. 13-WEEK STUDY IN F344/N RATS: Groups of 10 male and 10 female F344/N rats were exposed to pyridine in drinking water at concentrations of 0, 50, 100, 250, 500, or 1,000 ppm (equivalent to average daily doses of 5, 10, 25, 55, or 90 mg pyridine/kg body weight). Two females exposed to 1,000 ppm died during week 1. Final mean body weights of 1,000 ppm males and females and 500 ppm females were significantly less than controls. Water consumption by female rats exposed to 1,000 ppm was less than that by controls. At study termination, evidence of anemia persisted in the 500 and 1,000 ppm males and all exposed groups of females. There was evidence of hepatocellular injury and/or altered hepatic function demonstrated by increased serum alanine aminotransferase and sorbitol dehydrogenase activities and bile acid concentrations in 500 and 1,000 ppm rats. The estrous cycle length of 1,000 ppm females was significantly longer than that of the controls. Liver weights of males and females exposed to 250 ppm or greater were significantly greater than controls. In the liver, the incidences of centrilobular degeneration, hypertrophy, chronic inflammation, and pigmentation were generally increased in 500 and 1,000 ppm males and females relative to controls. In the kidney, the incidences of granular casts and hyaline degeneration (hyaline droplets) were significantly increased in 1,000 ppm males and slightly increased in 500 ppm males; these lesions are consistent with 2u-globulin nephropathy. Additionally, there were increased incidences and/or severities of protein casts, chronic inflammation, mineralization, and regeneration primarily in 500 and 1,000 ppm males. 13-WEEK STUDY IN MALE WISTAR RATS: Groups of 10 male Wistar rats were exposed to pyridine in drinking water at concentrations of 0, 50, 100, 250, 500, or 1,000 ppm (equivalent to average daily doses of 5, 10, 30, 60, or 100 mg/kg). One male rat exposed to 500 ppm died during week 1. Final mean body weights of rats exposed to 250, 500, or 1,000 ppm were significantly less than those of the controls. Water consumption by rats exposed to 1,000 ppm was lower than that by controls. There was evidence of hepatocellular injury and/or altered hepatic function in the 500 and 1,000 ppm groups, similar to that observed in the 13-week study in F344/N rats. Incidences of centrilobular degeneration, hypertrophy, chronic inflammation, and pigmentation in the liver of rats exposed to 500 or 1,000 ppm were significantly increased relative to controls. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were exposed to pyridine in drinking water at concentrations of 0, 50, 100, 250, 500, or 1,000 ppm (equivalent to average daily doses of 10, 20, 50, 85, or 160 mg/kg for males and 10, 20, 60, 100, or 190 mg/kg for females). One female mouse exposed to 250 ppm died during week 2. Final mean body weights of female mice exposed to 1,000 ppm were significantly less than those of controls. Water consumption by exposed female mice was lower than that by controls at week 1 but generally slightly higher than controls at week 13. Sperm motirm motility in exposed male mice was significantly decreased relative to controls. Liver weights were significantly increased relative to controls in males exposed to 100 ppm or greater and in 250 and 500 ppm females. No chemical-related lesions were observed in male or female mice. 2-YEAR STUDY IN F344/N RATS: Groups of 50 male and 50 female F344/N rats were exposed to pyridine in drinking water at concentrations of 0, 100, 200, or 400 ppm (equivalent to average daily doses of 7, 14, or 33 mg/kg) for 104 (males) or 105 (females) weeks. Survival, Body Weights, and Water Consumption Survival of exposed males and females was similar to that of controls. Mean body weights of 400 ppm males and females were generally less than those of the controls throughout the study, and those of 200 ppm males and females were less during the second year of the study. Water consumption by males and females exposed to 200 or 400 ppm was generally greater than that by controls. Pathology Findings Incidences of renal tubule adenoma and renal tubule adenoma or carcinoma (combined) in male rats exposed to 400 ppm were significantly increased compared to controls and exceeded the historical control ranges. The findings from an extended evaluation (step section) of the kidneys did not reveal additional carcinomas, but additional adenomas were observed in each group of males. In the standard evaluation, an increased incidence of renal tubule hyperplasia was observed in 400 ppm males compared to controls. Incidences of mononuclear cell leukemia in female rats were significantly increased in the 200 and 400 ppm groups, and the incidence in the 400 ppm group exceeded the historical control range. Exposure concentration-related nonneoplastic liver lesions were observed in males and females, and the incidences were generally increased in groups exposed to 400 ppm. These included centrilobular cytomegaly, cytoplasmic vacuolization, periportal fibrosis, fibrosis, centrilobular degeneration and necrosis, and pigmentation. Bile duct hyperplasia occurred more often in exposed females than in controls. 2-YEAR STUDY IN MALE WISTAR RATS: Groups of 50 male Wistar rats were exposed to pyridine in drinking water at concentrations of 0, 100, 200, or 400 ppm (equivalent to average daily doses of 8, 17, or 36 mg/kg) for 104 weeks. Survival, Body Weights, and Water Consumption Survival of rats exposed to 200 or 400 ppm was significantly less than that of the controls. Mean body weights of rats exposed to 100, 200, or 400 ppm were significantly less than controls. Water consumption was similar by control and exposed rats. Pathology Findings The incidence of testicular interstitial cell adenoma in rats exposed to 400 ppm was significantly increased compared to controls. Incidences of interstitial cell hyperplasia were observed in control and exposed groups and were slightly, but not significantly, increased in rats exposed to 200 or 400 ppm. Severity of nephropathy was marked in all groups, and additional evidence of kidney disease, including mineralization in the glandular stomach, parathyroid gland hyperplasia, and fibrous osteodystrophy, was observed in 100 and 200 ppm rats. The incidences of hepatic centrilobular degeneration and necrosis, fibrosis, periportal fibrosis, and/or pigmentation were increased in one or more exposed groups. 2-YEAR STUDY IN MICE: Groups of 50 male B6C3F1 mice were exposed to pyridine in drinking water at concentrations of 0, 250, 500, or 1,000 ppm (equivalent to average daily doses of 35, 65, or 110 mg/kg) for 104 weeks, and groups of 50 female B6C3F1 mice were exposed to pyridine in drinking water at concentrations of 0, 125, 250, or 500 ppm (equivalent to average daily doses of 15, 35, or 70 mg/kg) for 105 weeks. Survival, Body Weights, and Water Consumption Survival of exposed males and females was similar to that of the controls. Mean body weights of 250 and 500 ppm females were less than controls. Water consumption by males exposed to 250 or 500 ppm was generally greater than that by controls during the last year of the study; male mice exposed to 1,000 ppm consumed less water than controls throughout the study. Water consumption by exposed females was generally lower than that by controls during the first year of the study, but greater than controls during the second year. Pathology Findings Hepatocellular neoplasms, including hepatoblastomas, in exposed male and female mice were clearly related to pyridine exposure. Additionally, many mice had multiple hepatocellular neoplasms. The incidences of hepatocellular neoplasms in exposed males and females generally exceeded the historical control ranges for drinking water studies. Neoplasms from control mice, 1,000 ppm males, and 500 ppm females were negative when stained for p53 protein. GENETIC TOXICOLOGY: Pyridine was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 or in L5178Y mouse lymphoma cells, with or without S9 metabolic activation, and it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. Pyridine was tested for induction of sex-linked recessive lethal mutations in adult male Drosophila melanogaster, and mixed results were obtained. In one experiment, administration by injection gave negative results, but feeding produced an equivocal response. A second experiment generated negative results by injection and feeding. A third experiment showed significant increases in sex-linked recessive lethal mutations in flies treated with pyridine by injection but not by feeding. Overall, results of the sex-linked recessive lethal mutations test in Drosophila melanogaster were considered negative by feeding and equivocal by injection. Results of a single reciprocal translocation test in male Drosophila melanogaster were negative. No induction of chromosomal aberrations or micronuclei was noted in bone marrow cells of male mice administered pyridine via intraperitoneal injection. CONCLUSIONS: Under the conditions of these 2-year drinking water studies, there was some evidence of carcinogenic activity of pyridine in male F344/N rats based on increased incidences of renal tubule neoplasms. There was equivocal evidence of carcinogenic activity of pyridine in female F344/N rats based on increased incidences of mononuclear cell leukemia. There was equivocal evidence of carcinogenic activity in male Wistar rats based on an increased incidence of interstitial cell adenoma of the testis. There was clear evidence of carcinogenic activity of pyridine in male and female B6C3F1 mice based on increased incidences of malignant hepatocellular neoplasms. In F344/N rats, exposure to pyridine resulted in increased incidences of centrilobular cytomegaly and degeneration, cytoplasmic vacuolization, and pigmentation in the liver of males and females; periportal fibrosis, fibrosis, and centrilobular necrosis in the liver of males; and bile duct hyperplasia in females. In male Wistar rats, pyridine exposure resulted in increased incidences of centrilobular degeneration and necrosis, fibrosis, periportal fibrosis, and pigmentation in the liver, and, secondary to kidney disease, mineralization in the glandular stomach and parathyroid gland hyperplasia. Synonyms: Azabenzene, azine
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PMID:NTP Toxicology and Carcinogenesis Studies of Pyridine (CAS No. 110-86-1) in F344/N Rats, Wistar Rats, and B6C3F1 Mice (Drinking Water Studies). 1257 3

After several weeks of treatment, levels of alanine aminotransferase (ALT) increase in 50% of patients treated with tacrine for Alzheimer's disease. We looked for progressive effects on DNA to explain delayed toxicity. We first studied the in vitro effects of tacrine on DNA replication and topoisomerase-mediated DNA relaxation. We then treated mice with doses of tacrine reproducing the human daily dose on a body area basis and studied the effects of tacrine administration for up to 28 days on hepatic DNA, mitochondrial function, and cell death. In vitro, tacrine impaired DNA polymerase gamma-mediated DNA replication and also poisoned topoisomerases I and II to increase the relaxation of a supercoiled plasmid. In vivo, administration of tacrine markedly decreased incorporation of [(3)H]thymidine into mitochondrial DNA (mtDNA), progressively and severely depleted mtDNA, and partly unwound supercoiled mtDNA into circular mtDNA. Incorporation of [(3)H]thymidine into nuclear DNA (nDNA) was barely decreased, and nDNA levels were unchanged. After 12 to 28 days of treatment, administration of tacrine increased p53, Bax, mitochondrial permeability transition, cytosolic cytochrome c, and caspase-3 activity and triggered hepatocyte apoptosis and/or necrosis. In conclusion, the intercalating drug tacrine poisons topoisomerases and impairs DNA synthesis. Tacrine has been shown to accumulate within mitochondria, and it particularly targets mtDNA. After several weeks of treatment, the combination of severe mtDNA depletion and a genotoxic stress enhancing p53, Bax, and permeability transition trigger hepatocyte necrosis and/or apoptosis.
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PMID:Tacrine inhibits topoisomerases and DNA synthesis to cause mitochondrial DNA depletion and apoptosis in mouse liver. 1293 98

Obesity is a major health problem in industrialized societies, and fatty liver disease (hepatic steatosis) is common in obese individuals. Oxidative stress originating from increased intracellular levels of fatty acids has been implicated as a cause of hepatocellular injury in steatosis, although the precise mechanisms remain to be elucidated. p53, widely known as a tumor suppressor, has been shown often to be activated in stressed cells, inducing cell cycle arrest or death. Here we demonstrate that p53 is involved in the molecular mechanisms of hepatocellular injury associated with steatosis. We found that p53 in the nucleus is induced in the liver from two mouse models of fatty liver disease, ob/ob and a transgenic mouse model that overexpresses an active form of sterol regulatory element-binding protein-1 in the liver (TgSREBP-1), the one with obesity and the other without obesity. This activation of the p53 pathway leads to the elevation of p21 mRNA expression, which can be considered an indicator of p53 activity, because ob/ob mice lacking p53 generated by targeting gene disruption exhibited the complete restoration of the p21 elevation to wild type levels. Consistent with these results, the amelioration of hepatic steatosis caused by Srebp-1 gene disruption in ob/ob mice lowered the p21 expression in a triglyceride content-dependent manner. Moreover, p53 deficiency in ob/ob mice resulted in a marked improvement of plasma alanine aminotransferase levels, demonstrating that p53 is involved in the mechanisms of hepatocellular injury. In conclusion, we revealed that p53 plays an important role in the pathogenesis of fatty liver disease.
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PMID:p53 involvement in the pathogenesis of fatty liver disease. 1498 41


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