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Apoptotic Hepatocytes (apoptotic + hepatocyte)
Selected AbstractsGrowth potential of adult hepatocytes in mammals: Highly replicative small hepatocytes with liver progenitor-like traitsDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2 2007Katsutoshi Yoshizato The liver is one of the few organs that is capable of completely regenerating itself without using a stem cell population. When damaged, growth factors and cytokines are released, stimulating terminally differentiated adult hepatocytes and making them re-enter the cell cycle. We have been developing a series of studies on the growth potential of rat and human hepatocytes to identify a population of hepatocytes that is responsible for the regeneration of the injured liver. For this purpose, we established an appropriate culture method for hepatocytes by which growth and differentiation capacities are practically examined under various experimental conditions. This in vitro assay system allows us to identify small hepatocytes that are prominently replicative compared to large hepatocytes. Non-parenchymal cells play critical roles in the proliferation of small hepatocytes. These hepatocytes are present in both rat and human liver and are located in portal regions there. Phenotypic features were examined at morphological and gene/protein levels in detail, which showed the phenotypic plasticity in vitro. Mammalian liver includes a population of small hepatocytes in normal adults with a minute occupancy rate. We speculate that small hepatocytes play a role in regenerating the injured liver and in compensating for apoptotic hepatocytes in the physiological turnover of hepatocytes. [source] Moderate Alcohol Consumption Aggravates High-Fat Diet Induced Steatohepatitis in RatsALCOHOLISM, Issue 3 2010Yan Wang Background:, Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition. Methods:, Sprague-Dawley rats were first fed ad libitum with Lieber-DeCarli high-fat diet (71% energy from fat) for 6 weeks to induce NASH, as demonstrated previously. Afterwards, these rats were continuously fed with high-fat diet (HFD, 55% total energy from fat) or high fat plus alcohol diet (HFA, 55% energy from fat and 16% energy from alcohol) for an additional 4 weeks. Pathological lesions including fat accumulation and inflammatory foci in liver were examined and graded. Lipid peroxidation and apoptotic hepatocytes in the liver were assessed. The mRNA expressions of tumor necrosis factor-, (TNF,) and TNF receptor 1 (TNF-R1), Fas death receptor (Fas) and Fas ligant (FasL), IL-1, and IL-12 were determined by real-time PCR. Protein levels of total and cleaved caspase-3, CYP2E1, Bax, and Bcl-2 were measured by western blotting. Results:, The number of hepatic inflammatory foci and apoptotic hepatocytes were significantly increased in rats fed with HFA as compared with those in HFD-fed rats. The aggravated inflammatory response and cellular apoptosis mediated by HFA were associated with elevated mRNA expression of Fas/FasL and cleaved caspase-3 protein. Although no significant differences were observed between HFD and HFA groups, the levels of lipid peroxidation, Bax and Bcl-2 protein concentration, and mRNA levels of other inflammatory cytokines were significantly higher in these 2 groups than those in the control group. Conclusions:, These data suggest that even moderate alcohol consumption can cause more hepatic inflammation and cellular apoptosis in a pre-existing NASH condition. [source] Dilinoleoylphosphatidylcholine Reproduces the Antiapoptotic Actions of Polyenylphosphatidylcholine Against Ethanol-Induced Hepatocyte ApoptosisALCOHOLISM, Issue 6 2003Ki M. Mak Background: Polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated phosphatidylcholines extracted from soybeans, attenuates hepatocyte apoptosis induced by ethanol feeding of rats. Our aims were to evaluate whether dilinoleoylphosphatidylcholine (DLPC), the main component of PPC, reproduces the antiapoptotic actions of PPC against alcohol-induced apoptosis and to identify the apoptotic proteins that are affected by PPC and DLPC. Methods: Rats were fed Lieber-DeCarli liquid diets containing ethanol (35% of energy) or an isocaloric amount of carbohydrate for 4 weeks. Another group of rats were given the ethanol diet supplemented with PPC (3 g/liter) or DLPC (1.5 and 3 g/liter). Hepatocyte apoptosis was assessed by terminal transferase-mediated dUTP nick end labeling staining and by caspase 3 enzyme activity. Activity of caspases 3 and 9 was assayed by using fluorogenic peptide substrates. Cytochrome c was quantified by enzyme-linked immunosorbent assay. The protein contents of cytochrome c, procaspase 3, caspase 3, Bcl-xL, and Bax were analyzed by Western blot and quantified by densitometry. Lobular localization of active caspase 3 was examined by immunoperoxidase staining. Results: PPC and DLPC decreased ethanol-induced increases in hepatocyte apoptosis, cytosolic cytochrome c, and caspase 3 content and its activity. Caspase 3 activity correlated with the number of apoptotic hepatocytes. Active caspase 3 was present predominantly in perivenular hepatocytes, and ethanol feeding extended it to lobular hepatocytes; this ethanol effect was reduced by PPC and DLPC. Ethanol significantly decreased Bcl-xL in homogenate, mitochondria, and cytosol, and there was a trend for increased Bcl-xL in these fractions after PPC and DLPC supplementation. Microsomal Bcl-xL did not differ between treatment groups. Bax was detected in homogenate and cytosol, and its level was not affected by ethanol. Conclusions: DLPC, at a dose contained in PPC, reproduces the antiapoptotic actions of PPC through a reduction in cytosolic cytochrome c concentration and caspase 3 activity, possibly in association with up-regulation of Bcl-xL expression. Because DLPC is a pure and well defined compound, it may be more suitable than PPC for intervention against alcohol-induced apoptosis. [source] Hepatocyte growth factor protects against Fas-mediated liver apoptosis in transgenic miceLIVER INTERNATIONAL, Issue 10 2009Hideyuki Suzuki Abstract Background: Apoptosis via the Fas/Fas ligand signalling system plays an important role in the development of various liver diseases. The administration of an agonistic anti-Fas antibody to mice causes massive hepatic apoptosis and fulminant hepatic failure. Several growth factors including hepatocyte growth factor (HGF) have been found to prevent apoptosis. Methods: In this study, we demonstrated the overexpression of HGF to have a protective effect on Fas-mediated hepatic apoptosis using a transgenic mice (Tg mice) model. Results: In HGF Tg mice, the elevation of alanine aminotransferase was dramatically inhibited at 12 and 24 h after the administration of 0.15 mg/kg anti-Fas antibody. HGF Tg mice showed a significantly lower number of apoptotic hepatocytes at 12 h compared with wild-type (WT) mice. Furthermore, 85% (six of seven) HGF Tg mice were able to survive after the administration of 0.3 mg/kg anti-Fas antibody, while none of the WT mice survived. The Bcl-xL expression was increased in HGF Tg mice, while there was no difference in the expression of Bax, Bid, Mcl-1 and bcl-2 between WT mice and HGF Tg mice. In addition, the HGF Tg mice showed more Akt phosphorylation than the WT mice both before and after the anti-Fas antibody injection. Conclusions: Taken together, our findings suggest that HGF protects against Fas-mediated liver apoptosis in vivo, and the upregulation of Bcl-xL via Akt activation may also play a role in the protective effects of HGF. [source] Seventh Day Syndrome , acute hepatocyte apoptosis associated with a unique syndrome of graft loss following liver transplantation,LIVER INTERNATIONAL, Issue 1 2001Muhammed Ashraf Memon Abstract:Aim: The aim of this study is to describe a unique 7th day syndrome (7DS), quite different from other causes of post-transplantation allograft dysfunction in a group of orthotopic liver transplant (OLT) patients who needed retransplantation. Methods: A retrospective analysis of 594 consecutive OLT over an 8-year period revealed that 10 patients developed allograft dysfunction approximately 7 days following an initially normal graft function. Results: The features included: (a) severe liver failure; (b) sudden peak of extremely high liver enzymes at approximately day 7; (c) serial liver biopsy findings of central lobular hemorrhage with minimal inflammatory cell infiltrate and (d) an explant with no evidence of vascular thrombosis. The biochemical and morphometric pathological data of these patients were compared with data of patitents who had early acute rejection (AR), hepatic artery thrombosis (HAT), primary non-function (PNF), severe sepsis and no dysfunction. Lastly, serial liver core biopsies and explants were tested for evidence of apoptosis, which revealed a significantly higher number of apoptotic hepatocytes in 7DS compared to all control groups. Conclusions: Seventh Day Syndrome is a distinct entity associated with early graft dysfunction characterized by a marked apoptosis of hepatocytes. Fas receptor activation or other pathways of program cell death may be implicated in occurrence of 7DS. [source] Fulminant Liver Failure After Vancomycin in a Sulfasalazine-Induced DRESS Syndrome: Fatal Recurrence After Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009M. Mennicke DRESS syndrome (drug rash with eosinophilia and systemic symptoms) is a rare drug hypersensitivity reaction with a significant mortality. We describe a 60-year-old man with polyarthritis treated with sulfasalazine who developed DRESS and fulminant liver failure after additional vancomycin treatment. Liver histology revealed infiltration of granzymeB+ CD3+ lymphocytes in close proximity to apoptotic hepatocytes. After a superurgent liver transplantation and initial recovery, the patient developed recurrent generalized exanthema and eosinophilia, but only moderate hepatitis. Histology showed infiltration of FasL+ lymphocytes and eosinophils in the transplanted liver. Treatment with high-dose methylprednisolone was unsuccessful. Postmortem examination revealed extensive necrosis of the liver transplant. This case report illustrates that patients with DRESS may develop fulminant liver failure and that DRESS recurrence can recur in the transplanted liver. Histological and immunological investigations suggest an important role of granzymeB and FasL mediated cell death in DRESS associated hepatitis. [source] | ||||||||||