Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy

Theocharis, Stamatios; Skopelitou, Antigone; Margeli, Alexandra; Pavlaki, K.; Kittas, Christos

doi:10.1007/bf02090193

Cited by 56 publications

(34 citation statements)

References 34 publications

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“…In addition, methylmalonic acid is produced by the hydrolysis of methylmalonyl-CoA, accumulated in the plasma and tissues, and excreted abnormally into the urine (methylmalonic aciduria) (1,2,16). It has been reported that methylmalonic acid, when accumulated in the liver, decreases respiratory activity by inhibiting the succinate dehydrogenase reaction (2, 7).…”

Section: Resultsmentioning

confidence: 99%

Abnormal Increase in the Expression Level of Proliferating Cell Nuclear Antigen (PCNA) in the Liver and Hepatic Injury in Rats with Dietary Cobalamin Deficiency

Nakao

Kono

Adachi

et al. 2006

J Nutr Sci Vitaminol

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Summary Dietary cobalamin (Cbl; vitamin B 12 ) deficiency resulted in severe growth retardation in rats, and body weight in the Cbl-deficient rats at 20 wk of age was significantly lower compared with the age-matched Cbl-sufficient control rats. In contrast, liver weight, when normalized to body weight, was greater in the Cbl-deficient rats than in the controls ( p Ͻ 0.05). The expression level of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, in the liver was significantly enhanced in the deficient rats, suggesting that cell proliferation is abnormally activated in the liver under Cbl-deficient conditions. In addition, plasma alanine aminotransferase (ALT) activity, a marker for hepatic injury, was also significantly elevated in the deficient rats. When L -carnitine, which is used clinically for the treatment of Cbl-deficient patients with methylmalonic aciduria, was administered to the Cbl-deficient rats by intraperitoneal injection twice per day for 2 wk (each 0.5 mmol), the amount of methylmalonic acid excreted into the urine was significantly reduced, and the plasma ALT activity was lowered to a normal level. However, the PCNA expression in the liver was barely influenced by the treatment with carnitine. In contrast, when the deficient rats were fed an L -methionine-supplemented diet (4 g of L -methionine per kg of the diet) for 2 wk, the increased expression of PCNA was normalized.

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Section: Resultsmentioning

confidence: 99%

Abnormal Increase in the Expression Level of Proliferating Cell Nuclear Antigen (PCNA) in the Liver and Hepatic Injury in Rats with Dietary Cobalamin Deficiency

Nakao

Kono

Adachi

et al. 2006

J Nutr Sci Vitaminol

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“…Immunohistochemical detection of PCNA is a convenient and commonly used method to grade proliferative activity in various tissues. PCNA expression is closely correlated with the S-phase of the cell cycle (17). Fig.…”

Section: Effect Of Partial Hepatectomy On Hepatic Polyamine Pools In mentioning

confidence: 85%

A Polyamine Analogue Prevents Acute Pancreatitis and Restores Early Liver Regeneration in Transgenic Rats with Activated Polyamine Catabolism

Räsänen

Alhonen

Sinervirta

et al. 2002

Journal of Biological Chemistry

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We recently generated a transgenic rat model for acute pancreatitis, which was apparently caused by a massive depletion of pancreatic polyamines spermidine and spermine due to inducible activation of their catabolism (Alhonen, L., Parkkinen, J. J., Keinä nen, T., Sinervirta, R., Herzig, K. H., and Jä nne, J. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 8290 -8295). When subjected to partial hepatectomy, these animals showed striking activation of polyamine catabolism at 24 h postoperatively with a profound decrease in hepatic spermidine and spermine pools and failure to initiate liver regeneration. Here we show that pancreatitis in this model could be totally prevented, as judged by histopathology and plasma ␣-amylase activity, by administration of 1-methylspermidine, a metabolically stable analogue of spermidine. Similarly, the analogue, given prior to partial hepatectomy, restored early liver regeneration in the transgenic rats, as indicated by a dramatic increase in the number of proliferating cell nuclear antigen-positive hepatocytes from about 1% to more than 40% in response to the drug. The present results suggest that the extremely high concentration of spermidine in the pancreas, in fact the highest in the mammalian body, may have a critical role in maintaining organ integrity. The failure to initiate liver regeneration in the absence of sufficient hepatic polyamine pools similarly indicates that polyamines are required for proper commencement of the regenerative process.The polyamines spermidine and spermine and their precursor putrescine are intimately associated with growth and differentiation of mammalian cells, yet their exact cellular functions have not been solved (1). In attempts to elucidate the physiological roles of the polyamines, we have generated a number of transgenic mouse and rat lines with genetically altered polyamine metabolism. The activation of polyamine biosynthesis through an overexpression of ornithine decarboxylase brings about many interesting phenotypic changes, such as male infertility (2, 3), yet these studies are complicated by the fact that overexpression of ornithine decarboxylase only expands tissue putrescine pools as the latter diamine is not further converted to spermidine and spermine (4, 5). Much more severe distortion of tissue polyamine pools has been achieved by activation of polyamine catabolism through an overexpression of spermidine/spermine N 1 -acetyltransferase (SSAT) 1 in transgenic rodents. The latter enzyme catalyzes the rate-controlling reaction in the catabolism of spermidine and spermine. After being acetylated, spermidine is converted to putrescine and spermine to spermidine by the action of polyamine oxidase (6). Overexpression of SSAT in transgenic rodents results in profound changes in tissue polyamine pools, such as the massive accumulation of putrescine, appearance of N 1 -acetylspermidine, and decreases in spermidine and/or spermine pools (7). The alterations in polyamine homeostasis are accompanied by bizarre phenotypic changes, such as the earl...

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“…Liver regeneration after the surgical procedure was immunohistochemically assessed as previously described in the literature [9,10] . Briefly, 4-m thick sections of each regenerating remnant liver specimen were deparaffinized and mounted on slides coated with poly-L -lysine.…”

Section: Immunohistochemical Test Results For Proliferating Cell Nuclmentioning

confidence: 99%

“…One section from each specimen was semiquantitatively evaluated for intensity of PCNA staining using a four-tiered scale , with immunohistochemical scoring as follows: grade 0: no staining, grade 1: 1-30% staining, grade 2: 31-65% staining, grade: 3: 66-100% staining [9,10] .…”

Section: Immunohistochemical Test Results For Proliferating Cell Nuclmentioning

confidence: 99%

Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

Yuceturk

Yağmurdur²,

Gür

et al. 2007

Eur Surg Res

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Objectives: The aim of this study was to investigate the effect of heparin on TNF-α and interleukin (IL)-6 levels and the complement system in liver regeneration in a murine model. Materials and Methods: 32 Wistar albino female rats weighing between 180 and 250 g were included in the study. The rats were divided into four groups as follows: group 1, treated with partial (50%) hepatectomy and intravenous heparin 1,000 IU/kg in repeated daily doses; group 2, treated with sham operation and intravenous heparin 1,000 IU/kg in repeated daily doses; group 3, treated with partial (50%) hepatectomy, and group 4 (controls), treated with only sham operation. Before the surgical intervention and after a general anesthetic had been administered to all rats, blood was taken from the left ventricle of each rat, and each sample was assessed to determine total complement hemolytic activity (CH₅₀/ml). On the 5th postoperative day, blood was taken to assess CH₅₀ activity and the levels of TNF-α and IL-6 via ELISA. Each rat was then killed by decapitation after which gravimetric analysis and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) were performed. Results: Serum CH₅₀ activity of group 1 was 4% as compared to 51% in group 3 (p = 0.01). The serum TNF-α level of group 1 was 43 pg/ml as compared to 86 pg/ml in group 3 (p = 0.002). The serum IL-6 level of group 1 was 19 pg/ml as compared to 44 pg/ml in group 3 (p = 0.02). The serum IL-6 level of group 2 was 4 pg/ml as compared to 44 pg/ml in group 3 (p = 0.005). According to the results of gravimetric analysis, the mean regeneration rate of group 1 was 4.4% as compared to 22% of group 3 (p = 0.001). The mean PCNA index values of group 2 was the highest of all groups (p = 0.01). However, the mean PCNA index value of group 1 was the lowest of all groups (p = 0.01). Conclusion: Because of its anti-inflammatory action via the complement system, heparin produced an unfavorable effect on liver regeneration.

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Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy

Cited by 56 publications

References 34 publications

Abnormal Increase in the Expression Level of Proliferating Cell Nuclear Antigen (PCNA) in the Liver and Hepatic Injury in Rats with Dietary Cobalamin Deficiency

Abnormal Increase in the Expression Level of Proliferating Cell Nuclear Antigen (PCNA) in the Liver and Hepatic Injury in Rats with Dietary Cobalamin Deficiency

A Polyamine Analogue Prevents Acute Pancreatitis and Restores Early Liver Regeneration in Transgenic Rats with Activated Polyamine Catabolism

Role of Heparin on TNF-α and IL-6 Levels in Liver Regeneration after Partial Hepatic Resection

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