Purification of human liver guanase and characterization of antibody against it by immunoblotting

Ito, Susumu; Iwasaki, Akiharu; Mizobuchi, Mieko; Matsuda, Yoshiko

doi:10.1016/0009-9120(90)80021-a

Cited by 3 publications

(2 citation statements)

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“…The latter may be used either as an energy source, or be recycled to regenerate (deoxy)nucleosides [30]. Deamination reactions, which are independent of cofactors and essentially irreversible, may occur either before (for deoxyadenosine [31] and deoxycytidine [32]) or after (for deoxyguanosine [33]) phosphorolysis (see Fig. 1).…”

Section: The Role Of Catabolic Enzymesmentioning

confidence: 99%

“…1). Both nucleoside phosphorylysis and deamination occur in the liver [30][31][32][33] and the susceptibility of many of the 'first-generation' (deoxy)nucleoside analogues to these processes significantly limited their activity [2]. At the monophosphate level, salvage activity may be either abetted or opposed by nucleotidase activity.…”

Section: The Role Of Catabolic Enzymesmentioning

confidence: 99%

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Preclinical aspects of lamivudine and famciclovir against hepatitis B virus

Shaw

Locarnini

1999

Journal of Viral Hepatitis

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Chemotherapy for chronic hepatitis B virus (HBV) infection is inherently difficult for a variety of reasons that are related to unusual features of both HBV replication strategy and host cell metabolism. Previous attempts to treat chronic HBV infection using nucleoside analogues have been almost universally disappointing, but several recently developed nucleoside analogues have been identified as potent, non-toxic inhibitors of HBV replication. These fall into two broad categories: nucleosides having the 'unnatural' L-configuration, and deoxyguanosine analogues with modified-sugar configurations, represented by lamivudine and penciclovir respectively. Both lamivudine and penciclovir (in its orally available form, famciclovir) have progressed to phase III clinical trials against chronic HBV infection, with promising preliminary results. However, chemotherapy for chronic HBV is necessarily long term, which increases the risks for development of viral resistance and cumulative toxicity. Such risks might be minimized by the use of appropriate drug combinations, rational selection of which requires knowledge of the pharmacokinetics and mechanisms of action of the individual agents. An appreciation of cellular deoxynucleoside metabolism and its regulation, the complexities of which are still emerging, is an indispensable aid to understanding the biological activities of deoxynucleoside analogues. The modes of action of lamividine and penciclovir, and how these two deoxynucleoside analogues may interact in vitro and in vivo as inhibitors of HBV replication, are examined here in the context of cellular deoxynucleoside metabolism.

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Section: The Role Of Catabolic Enzymesmentioning

confidence: 99%

Section: The Role Of Catabolic Enzymesmentioning

confidence: 99%

Preclinical aspects of lamivudine and famciclovir against hepatitis B virus

Shaw

Locarnini

1999

Journal of Viral Hepatitis

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A histochemical and immunohistochemical investigation of guanase and nedasin in rat and human tissues

et al. 2006

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: Human guanase is known as a specific enzyme in the liver, kidney, and brain. However, its functional significance remains poorly understood. In addition, interestingly, a different organ distribution between humans and rats was suggested. Here, we performed immunohistochemical staining with anti-human nedasin(neuronal and endocrine discs large/SAP102 associated protein), whose sequence was identical to that of guanase, antibody and histochemical staining for guanase in normal tissues of rat and human liver, kidney, and small intestine, and compared the results. Guanase activity was observed uniformly in the rat hepatocytes, biliary epithelium and vascular endothelium cells, while it was localized to the hepatocytes and biliary epithelium in the human liver. When the histochemical staining for guanase and the immunohistochemical staining for nedasin were compared, the stained regions were different in the rat liver but were almost consistent in all human tissues. Totally consistent staining results were also obtained between rats and humans in the other organization except the liver. Based upon the research reports to date, the experiments on guanase and nedasin in rat organs performed in this study are considered to have important implications in the investigation of their physiological significance. J. Med. Invest. 53 : 246-254, August, 2006

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Histochemical and immunohistochemical investigation of guanase and nedasin in human tissues

et al. 2006

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: Guanase is known as an enzyme released from the liver. Recently, cloning and sequencing of the guanase gene were reported. In addition, almost simultaneously, it was reported that an unknown protein that binds to neuronal and endocrine lethal(1)-discs large (NE-dlg), one of the membrane-associated guanylate kinase homologues (MAGUK) family proteins involved in synaptic connection between neurons, was cloned and named nedasin (NE-dlg associated protein), whose sequence was almost identical to that of guanase. We immunostained fresh frozen sections of surgically removed human liver, kidney, and small intestine with anti-nedasin antibody, and simultaneously performed histochemical staining for guanase for comparison. Histochemically, guanase activity was observed in the cytoplasm of hepatocytes and biliary epithelium on the liver, in the mucosal epithelium on the small intestine, and in the proximal tubule on the kidney. Immunohistochemically, a brown discoloration due to DAB oxidation was seen in the cytoplasm of hepatocytes and biliary epithelium on the liver, in the proximal tubule but in the distal tubule a little on the kidney, in the mucosal epithelium on the small intestine. The stained region of the liver and the small intestine were different from that of the kidney. The different staining properties dependent on the organs were considered to be due to different isozymes. The physiological significance of guanase may vary with the isozymes, further studies are considered necessary.

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Purification of human liver guanase and characterization of antibody against it by immunoblotting

Cited by 3 publications

References 22 publications

Preclinical aspects of lamivudine and famciclovir against hepatitis B virus

Preclinical aspects of lamivudine and famciclovir against hepatitis B virus

A histochemical and immunohistochemical investigation of guanase and nedasin in rat and human tissues

Histochemical and immunohistochemical investigation of guanase and nedasin in human tissues

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