Glycoprotein catabolism in rat liver. Lysosomal digestion of iodinated asialo-fetuin

LaBadie, Jon Henry; Chapman, Kristi Peterson; Aronson, Nathan N.

doi:10.1042/bj1520271

Cited by 134 publications

(51 citation statements)

References 21 publications

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“…This is in marked contrast to galactose-terminated fetuin, orosomucoid, and (vl-antitrypsin which are rapidly catabolized after their uptake by rat or human liver (29)(30)(31). Thus, the hepatic metabolism of j3-hexosaminidase is fundamentally different from that of galactose-terminated glycoproteins.…”

Section: Discussionmentioning

confidence: 91%

Selective hepatic uptake of human β-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells

Steer

Kusiak

Brady

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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Intravenously administered 25I-labeled human l3-hexosaminidase A (P-N-acetylglucosaminidase; 2-acetamido-2-deoxy-p-D>glucoside acetamidodeoxyglucohydrolase, EC 3.2.1.30) was rapidly cleared from the circulation of rats and accumulated in the liver. When hepatic cells were subsequently isolated, the label was recovered from both sinusoidal cells and, The structure of the carbohydrate moiety of glycoproteins, glycoconjugates, and lysosomal glycosidases profoundly influences their survival in the mammalian circulation. Many glycoproteins are rapidly cleared by the mammalian liver by processes that appear to depend on specific hepatic glycoprotein recognition systems. Ashwell. and coworkers have identified a hepatic receptor that mediates the rapid clearance of galactose-terminated glycoproteins from the plasma (1). A second hepatic recognition system that mediates the clearance of glycoproteins with terminal N-acetylglucosamine or mannose residues has been described (2-4). Initial experiments showed that many highly purified lysosomal glycosidases including human and rat 3-glucuronidase, rat ,B-galactosidase, a-fucosidase, a-mannosidase, and N-acetyl-f-D-glucosaminidase are promptly cleared from plasma by a recognition system located in the liver (5, 6). Glycoproteins with terminal mannose or N-acetylglucosamine residues were potent inhibitors of the clearance of these lysosomal glycosidases, suggesting that the hepatic uptake of these enzymes is mediated by a receptor or receptors that recognize exposed N-acetylglucosamine or mannose residues (2, 7 (9) of a mannose/N-acetylglucosamine recognition system on rat alveolar macrophages. This paper describes an in vitro study on the mechanism of the selective hepatic uptake of a native lysosomal enzyme f-hexosaminidase A (f-N-acetylglucosaminidase; 2-acetamido-2-deoxy-f-D-glucoside acetamidodeoxyglucohydrolase, EC 3.2.1.30). The results demonstrate that the sinusoidal cells of the liver, and not the hepatocytes, are primarily responsible for the hepatic uptake of this lysosomal glycosidase. Furthermore, the results suggest that the uptake process is mediated by a cell surface receptor that is responsible for the recognition and clearance of mannose-terminated glycoproteins.MATERIALS AND METHODS Waymouth's medium 752/1 and heat-inactivated newborn calf serum were obtained from GIBCO. Krebs-Henseleit buffer was furnished by the National Institutes of Health Media Section. Bovine serum albumin (fraction V), mannan, and Hepes were obtained from Sigma. Pronase was purchased from Calbiochem, collagenase (type II) from Worthington, and metrizamide (analytical grade) from the Accurate Chemical and Scientific Company (Hicksville, NY).3-Hexosaminidase A was purified by a modification of the method of Tallman et al. (10). Concanavalin A-Sepharose (Pharmacia) affinity chromatography and butyl-agarose (Miles) hydrophobic interaction chromatography were incorporated in the procedure, and the ammonium sulfate precipitation step was eliminated. The product appeared homogeneous...

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Section: Discussionmentioning

confidence: 91%

Selective hepatic uptake of human β-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells

Steer

Kusiak

Brady

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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“…Asialoglycoproteins are recognized by receptors present on the surface of hepatocytes, transferred to lysosomes and finally degraded there [16,17]. Therefore, when FITC-labeled asialofetuin is injected intravenously, it is incorporated into liver lysosomes [6].…”

Section: Analysis Of Intralysosomal Degradation Of Fitc-labeled Asialmentioning

confidence: 99%

Effects of selective inhibition of cathepsin B and general inhibition of cysteine proteinases on lysosomal proteolysis in rat liver in vivo and in vitro

Ohshita

Nikawa

Towatari

et al. 1992

European Journal of Biochemistry

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Intraperitoneal administration of N-(~-tran~-pr0pylcarbamoyloxirane-2-carbonyl)-~-isoleucyl-~-proline (CA-074) to rats at a dose of 4 mg/100 g greatly inhibited cathepsin-B activity in both liver and kidney for at least 4 h. Its inhibitory effect was selective for cathepsin-B activity in the liver but not in the kidney. The effects of selective inhibition of cathepsin-B activity by CA-074 treatment, and general inhibition of cysteine proteinases by N-(~-3-t~~ns-carboxyoxirane-2-carbonyl)-~-leucyl-3-methylbutylamide (E-64-c) on the degradation of fluorescein isothiocyanate (F1TC)-labeled asialofetuin in liver lysosomes, were examined in vivo. Undegraded or partially degraded FITClabeled asialofetuin and its FITC-labeled degradation products were both found in the lysosomes and were easily separated by Sephadex G-25 column chromatography. The FITC-labeled degradation products were mainly lysine with an FITC-labeled c-amino group. Accumulation of undegraded or partially degraded FITC-labeled asialofetuin in the lysosomes was marked after E-64-c treatment, but slight after CA-074 treatment. Under the marked inhibition of general lysosomal cysteineproteinase activity by E-64-c or marked selective inhibition of cathepsin-B activity by CA-074 in vitro, degradation of FITC-labeled asialofetuin by disrupted lysosomes was analyzed on the basis of measurement of FTTC-labeled degradation products by Sephadex G-25 column chromatography. It was suppressed markedly but incompletely by E-64-c as well as by CA-074, but more weakly than by E-64-c. These results shows that E-64-sensitive cysteine proteinases are important in lysosomal protein degradation, but cathepsin B has only a role in part and that an E-64-resistant proteinase(s) may also be important.Many proteinases are present in lysosomes [l -31. These proteinases are probably all important in intralysosomal degradation of many species of proteins to amino acids, but their exact roles are unknown. Leupeptin is a potent inhibitor of cysteine proteinases and its injection into rats causes an increase in the density of lysosomes due to accumulation of undegraded proteins sequestered by autophagy and/or heterophagy tors should be useful for determining their roles in lysosomal protein degradation.leucyl-L-proline (CA-074), a derivative of N-(~-3-transcarboxyoxirane-2-carbonyl)-~-leucyl-4-guanidinobutylamide (E-64), has been designed and produced as a selective inhibitor of cathepsin B, and shown to inhibit cathepsin-B activity selectively both in vitro and in rat liver in vivo [7, 81. In this study, we examined the dose/response and time course of the effect of this compound on lysosomal cysteine-proteinase activity using synthetic substrates. We compared the effect of CA-074 on intralysosomal degradation of FITC-labeled asialofetuin with that of E-64. The results showed that lysosomes do not excrete FITC-labeled degradation products rapidly, and accumulate not only undegraded FITC-labeled asialofetuin but also FITC-labeled degradation products.We recently developed a method...

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“…It is well known that radiohalogenated peptides compared with radiometal chelated peptides exhibit different metabolic patterns and clearance routes (27)(28)(29)(30). The fast clearance of radiohalogenated peptides from normal tissues is sometimes an advantage for the development of imaging probes.…”

Section: Introductionmentioning

confidence: 99%

“…The significant hepatobiliary accumulation and retention of the 64 Cu-labeled compound is primarily due to the release of uncoordinated 64 Cu from the radio-labeled product by decomposition in the blood or trans-chelation in the liver (26). Further studies to optimize the biodistribution of 64 Cu-DOTA-NAPamide and to achieve better imaging quality are needed.It is well known that radiohalogenated peptides compared with radiometal chelated peptides exhibit different metabolic patterns and clearance routes (27)(28)(29)(30). The fast clearance of radiohalogenated peptides from normal tissues is sometimes an advantage for the development of imaging probes.…”

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confidence: 99%

Small-Animal PET of Melanocortin 1 Receptor Expression Using a 18F-Labeled -Melanocyte-Stimulating Hormone Analog

Cheng¹,

Zhang²,

Graves³

et al. 2007

Journal of Nuclear Medicine

103

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Abstract18 F-Labeled small synthetic peptides have emerged as attractive probes for imaging various molecular targets with PET. The α-melanocyte-stimulating hormone (α-MSH) receptor (melanocortin type 1 receptor [MC1R]) is overexpressed in most murine and human melanomas. It is a promising molecular target for diagnosis and therapy of melanomas. However, 18 F compounds have not been successfully developed for imaging the MC1R.Methods-In this study, an α-MSH analog, Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH 2 (NAPamide), was radiolabeled with N-succinimidyl-4-18 F-fluorobenzoate ( 18 F-SFB). The resulting radiopeptide was evaluated as a potential molecular probe for small-animal PET of melanoma and MC1R expression in melanoma xenografted mouse models.Results-The binding affinity of 19 F-SFB-conjugated NAPamide, 19 F-FB-NAPamide, was determined to be 7.2 ± 1.2 nM (mean ± SD) using B16/F10 cells and 125 I-(Tyr 2 )-[Nle 4 ,D-Phe 7 ]-α-MSH [ 125 I-(Tyr 2 )-NDP] as a radio-ligand. The biodistribution of 18 F-FB-NAPamide was then investigated in C57BL/6 mice bearing subcutaneous murine B16/F10 melanoma tumors with high expression of MC1Rs and Fox Chase Scid mice bearing human A375M melanoma with a relatively low number of MC1R receptors. Biodistribution experiments showed that tumor uptake values (percentage injected dose per gram of tumor [%ID/g]) of 18 F-FB-NAPamide were 1.19 ± 0.11 %ID/g and 0.46 ± 0.11 %ID/g, in B16/F10 and A375M xenografted melanoma at 1 h after injection, respectively. Furthermore, the B16/F10 tumor uptake was significantly inhibited by coinjection with excess α-MSH peptide (P < 0.05), indicating that 18 F-FB-NAPamide specifically recognizes the MC1R in living mice. Small-animal PET of 18 F-FB-NAPamide in mice bearing COPYRIGHT © 2007 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptB16/F10 and A375M tumors at 1 h after tail vein injection revealed good B16/F10 tumor-tobackground contrast and low A375M tumor-to-background ratios.Conclusion-18 F-FB-NAPamide is a promising molecular probe for α-MSH receptor-positive melanoma PET and warrants further study. Keywordsmelanoma; α-melanocyte-stimulating hormone; PET; imaging; 18 F Cutaneous malignant melanoma is one of the most lethal cancers. Its incidence is increasing rapidly, making it a significant public health problem in Europe and the United States (1,2). Although extensive research has been performed to develop novel strategies for systemic treatment of malignant melanoma, effective therapies are still not available. The most important approach for improvement of survival of patients with melanoma still remains early diagnosis, along with accurate staging of the extent of disease (3,4).Many molecular imaging agents have been evaluated for detection of melanoma.Currently, 18 F-FDG is widely used in staging melanoma. The sensitivity, specificity, and accuracy of 18 F-FDG PET for detecting recurrent melanoma range from 70% to 100% (3). However, when imaging patients with early-stage melanoma, whole-body 18 F-FDG PET shows ...

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Glycoprotein catabolism in rat liver. Lysosomal digestion of iodinated asialo-fetuin

Cited by 134 publications

References 21 publications

Selective hepatic uptake of human β-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells

Selective hepatic uptake of human β-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells

Effects of selective inhibition of cathepsin B and general inhibition of cysteine proteinases on lysosomal proteolysis in rat liver in vivo and in vitro

Small-Animal PET of Melanocortin 1 Receptor Expression Using a 18F-Labeled -Melanocyte-Stimulating Hormone Analog

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