Home About us Contact
|
Home About us Contact | ||
|
|
||
Rat Liver Regeneration (rat + liver_regeneration)
Selected AbstractsCyclin-dependent kinase 1 plays a critical role in DNA replication control during rat liver regeneration,HEPATOLOGY, Issue 6 2009Delphine Garnier Liver regeneration is a unique process to restore hepatic homeostasis through rapid and synchronous proliferation of differentiated hepatocytes. Previous studies have shown that hepatocyte proliferation is characterized by high expression levels of the "mitotic" cyclin-dependent kinase 1 (Cdk1) during S-phase compared to other mammalian cells. In the light of findings showing that Cdk1 compensates for the loss of Cdk2 and drives S-phase in Cdk2-deficient cells derived from Cdk2 knockout mice, we took advantage of the models of liver regeneration following partial hepatectomy and primary cultures of normal rat hepatocytes to further examine the involvement of Cdk1 during DNA replication in hepatocytes and to dissect specific cell cycle regulation in hepatocytes compared to control human foreskin fibroblasts. In hepatocytes, Cdk1 exhibited a biphasic activation pattern correlating S-phase and G2/M transition, bound to cyclin A or B1 and localized to the nucleus during DNA replication. Importantly, small interfering RNA (siRNA)-mediated silencing of Cdk1 led to a strong decrease in DNA synthesis without affecting centrosome duplication. Furthermore, in hepatocytes arrested by the iron chelator O-Trensox in early S-phase prior to DNA replication, Cdk1/cyclin complexes were active, while replication initiation components such as the minichromosome maintenance 7 (Mcm7) protein were loaded onto DNA. Moreover, Mcm7 expression and loading onto DNA were not modified by Cdk1 silencing. Conversely, in fibroblasts, Cdk1 expression and activation were low in S-phase and its silencing did not reduce DNA synthesis. Conclusion: Cdk1 is essential for DNA replication downstream formation of replication initiation complexes in hepatocytes but not in fibroblasts and, as such, our data exemplify crucial differences in the cell cycle regulation between various mammalian cell types. (HEPATOLOGY 2009.) [source] Relevance between lipid metabolism-associated genes and rat liver regenerationHEPATOLOGY RESEARCH, Issue 8 2008Cunshuan Xu Aim:, Lipids are important in constituting cell structure and participating in many biological processes, particularly in energy supplementation to cells. The aim of the present study is to elucidate the action of lipid metabolism-associated genes on rat liver regeneration (LR). Methods:, Lipid metabolism-associated genes were obtained by collecting website data and retrieving related articles, and their expression changes in the regenerating rat liver were checked by the Rat Genome 230 2.0 array. Results:, In total, 280 genes involved in lipid metabolism were proven to be LR-associated by comparing the gene expression discrepancy between the partial-hepatectomy and sham-operation groups. The initial and total expression numbers of these genes occurring in the initial phase, G0/G1 transition, cell proliferation, cell differentiation, and structure,functional rebuilding of LR were 128, 33, 135, 6, and 267, 147, 1026, 306, respectively, illustrating that these genes were initially expressed mainly in the initiation stage and functioned in different phases. Upregulation (850 times) and downregulation (749 times), as well as 25 types of expression patterns, showed that the physiological and biochemical activities were diverse and complicated in LR. Conclusion:, According to the results of the chip detection, it was presumed that fatty acid synthesis at 24,66 h, leukotriene and androgen synthesis at 16,168 h, prostaglandin synthesis at 2,96 h, triglyceride synthesis at 18,24 h, glycosphingolipid synthesis at 0.5,66 h, metabolism of phosphatidyl inositol and sphingomyelin at 2,16 h, and cholesterol catabolism at 30,168 h were enhanced. Throughout almost the whole LR, the genes participating in estrogen, glucocorticoid, and progesterone synthesis, and triglyceride catabolism were upregulated, while phospholipid and glycosphingolipid catabolism were downregulated. [source] K vitamins, PTP antagonism, and cell growth arrestJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2002Brian I. Carr The main function of K vitamins is to act as co-factors for ,-glutamyl carboxylase. However, they have also recently been shown to inhibit cell growth. We have chemically synthesized a series of K vitamin analogs with various side chains at the 2 or 3 position of the core naphthoquinone structure. The analogs with short thio-ethanol side chains are found to be more potent growth inhibitors in vitro of various tumor cell lines. Cpd 5 or [2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone] is one of the most potent. The anti-proliferation activity of these compounds is antagonized by exogenous thiols but not by non-thiol antioxidants. This suggests that the growth inhibition is mediated by sulfhydryl arylation of cellular glutathione and cysteine-containing proteins and not by oxidative stress. The protein tyrosine phosphatases (PTP) are an important group of proteins that contain cysteine at their catalytic site. PTPs regulate mitogenic signal transduction and cell cycle progression. PTP inhibition by Cpd 5 results in prolonged tyrosine phosphorylation and activation of several kinases and transcription factors including EGFR, ERK1/2, and Elk1. Cpd 5 could activate ERK1/2 either by signaling from an activated EGFR, which is upstream in the signaling cascade, or by direct inhibition of ERK1/2 phosphatase(s). Prolonged ERK1/2 phosphorylation strongly correlates with Cpd 5-mediated growth inhibition. Cpd 5 can also bind to and inhibit the Cdc25 family of dual specific phosphatases. As a result, several Cdc25 substrates (Cdk1, Cdk2, Cdk4) involved in cell cycle progression are tyrosine phosphorylated and thereby inhibited by its action. Cpd 5 could also inhibit both normal liver regeneration and hepatoma growth in vivo. DNA synthesis during rat liver regeneration following partial hepatectomy, transplantable rat hepatoma cell growth, and glutathione-S-transferase-pi expressing hepatocytes after administration of the chemical carcinogen diethylnitrosamine, are all inhibited by Cpd 5 administration. The growth inhibitory effect during liver regeneration and transplantable tumor growth is also correlated with ERK1/2 phosphorylation induced by Cpd 5. Thus, Cpd 5-mediated inhibition of PTPs, such as Cdc25 leads to cell growth arrest due to altered activity of key cellular kinases involved in signal transduction and cell cycle progression. This prototype K vitamin analog represents a novel class of growth inhibitor based upon its action as a selective PTP antagonist. It is clearly associated with prolonged ERK1/2 phosphorylation, which is in contrast with the transient ERK1/2 phosphorylation induced by growth stimulatory mitogens. © 2002 Wiley-Liss, Inc. [source] | ||||||||||