Phosphorylase: A New Isozyme in Rat Hepatic Tumors and Fetal Liver

Sato, Kei; Morris, Harold P.; Weinhouse, Sidney

doi:10.1126/science.178.4063.879

Cited by 58 publications

(20 citation statements)

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“…Comparative electrophoretic and immunological studies of the enzymes isolated from MH 3924A and ClI cells with those isolated from liver and brain showed that the enzyme expressed in the two cell lines exhibited characteristics similar to those of the brain isoenzyme, which, on the other hand, has been described to be closely related to the enzyme expressed in fetal liver or in 14-day whole embryo [15,[20][21][22]. The enzymes from the cell lines and from brain could easily be separated electrophoretically from the liver enzyme in native homogeneous and gradient gels, owing to differences in mobility (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Some years ago, Sato and co-workers [2,[20][21][22] described the occurrence of a phosphorylase isoenzyme in transplantable rat hepatomas, which was different from the liver isoenzyme but exhibited similar electrophoretic mobility to the brain-or fetaltype enzyme, and cross-reaction with antibodies raised against the brain isoenzyme. So far, only the b-form of the phosphorylase isoenzyme from Novikoff hepatoma has been isolated and partly characterized biochemically and immunologically [21,22]; extracts from other hepatomes, e.g.…”

Section: Introductionmentioning

confidence: 99%

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Glycogen phosphorylase isoenzymes from hepatoma 3924A and from a non-tumorigenic liver cell line. Comparison with the liver and brain enzymes

Mayer

Seelmann-Eggebert

Letsch

1992

Biochemical Journal

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Glycogen phosphorylase isoenzymes were isolated from normal rat liver, rat brain, the glycogen-poor Morris hepatoma (MH) 3924A, and the glycogen-rich non-tumorigenic liver cell line C1I. Electrophoretic and immunological characterization of the enzymes showed that tumour and C1I cells expressed a phosphorylase isoform similar to the brain type; the liver type was not detectable. All enzymes were obtained as dimers; the Mr of the subunits was 96000 (liver), 93000 (brain and MH 3924A) and 92000 (C1I). Isoelectric focusing revealed a main band of pI 6.34 for liver phosphorylase a, pl 5.67 for the enzymes from MH 3924A and brain, and pI 5.68 for CII phosphorylase. Partial kinetic characterization of the AMP-independent forms of the isoenzymes yielded Km values for glucose 1-phosphate of 3.5 + 0.5 mm (liver), 3.9 mm (brain), 1.9 + 0.3 mm (MH 3924A) and 2.5 + 0.5 mm (C1I); Km values for glycogen were 0.4 mM (liver) and 0.3 mm (MH 3924A and C1I), calculated as glucose equivalents. The AMP-independent phosphorylase was inhibited by glucose 6-phosphate (Glc6P) with Ki values of 0.32 + 0.03 mm (C1I), 0.50 + 0.04 mm (MH 3924A) and -5 mM (brain). The inhibition could be abolished by 1 mM-AMP, indicating that AMP and Glc6P may partially compete for the same site on the protein. Liver phosphorylase a was not inhibited by up to 25 mM-Glc6P. In contrast with liver and brain isoenzymes, phosphorylase from the cell lines was not affected by NaF and Na2SO4. The data show that both the hepatocellular carcinoma and the non-malignant immortalized liver cells express a phosphorylase isoform different from the liver type. Furthermore, there is some evidence that the enzyme from MH 3924A and C1I cells is distinct from brain phosphorylase a, in spite of electrophoretic and immunological resemblance, and that this isoenzyme is subject to altered metabolic regulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glycogen phosphorylase isoenzymes from hepatoma 3924A and from a non-tumorigenic liver cell line. Comparison with the liver and brain enzymes

Mayer

Seelmann-Eggebert

Letsch

1992

Biochemical Journal

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“…Therefore, glycogen accumulation in the adult hepatocyte site. Earlier studies using electrophoretic separation of phosphoexposed to medium glucose levels equal to or substantially higher rylase isoz~mes suggested that fetal rat liver contained largely the than that normally found in vivo may be readily explained by phosphorylase isozyme found postnatally only in brain and in complementary increased active glycogen synthase and decreased some neoplastic tissues (42)(43)(44). The nature of glucose control active phosphorylase.…”

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confidence: 99%

Glycogenesis in the Cultured Fetal and Adult Rat Hepatocyte Is Differently Regulated by Medium Glucose

et al. 1992

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“…The physiological roles of muscle and liver GP are to provide fuel for energy production (to produce the energy required for muscle contraction) and to ensure a constant supply of glucose to extrahepatic tissues, respectively. However, the physiological role of BGP is poorly understood, although BGP is generally considered to be involved in the provision of emergency glucose supplies during stressful and/or ischemic periods [2,4,6,7]. In addition, it has been demonstrated that BGP is the major isoform of GP found in fetal tissue and tumor tissue, and BGP is identical to fetal-type GP (FGP) [6,7].…”

Section: Introductionmentioning

confidence: 99%

Fetal-type Glycogen Phosphorylase Expression in Intestinal Metaplasia as a Predictor of the Development of Gastric Cancer

Ikeshima¹,

Horino²,

Morinaga³

et al. 2018

Biomark J

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Glycogen phosphorylase (GP; EC 2.4.1.1) plays a central role in the mobilization of carbohydrate reserves in a wide variety of organs and tissues. There are three major isoforms of mammalian GP; i.e., the muscle, liver, and brain isoforms. The physiological roles of muscle and liver GP are to provide fuel for energy production (to produce the energy required for muscle contraction) and to ensure a constant supply of glucose to extra hepatic tissues, respectively. However, the physiological role of brain GP (BGP) is poorly understood. It has been demonstrated that BGP is the major isoform of GP found in fetal tissue and tumor tissue, and BGP is identical to fetal-type GF (FGP).We have demonstrated that the significant enzymatic activity of FGP in the gastric carcinoma and proliferating cells of particular Intestinal Metaplasia (IM). We studied 136 specimens with gastric carcinoma and the adjacent IM using specific anti-FGP antibody. FGP was expressed in 80% of the intestinal type and 19% of the diffuse type of carcinoma and in 88% and 42% in the generative zone of IM adjacent to each type of cancer foci, respectively. The proportion of the positivity of FGP expression in the cancer and IM was significantly greater in intestinal type carcinoma than in diffuse type. In addition, according to the proliferating cell nuclear antigen labeling index analysis, IM with FGP expression (FGP-IM) were significantly higher in a proliferating state than in IM without FGP, and some of them were co-expressed accumulated p53 in the generative cells. These data indicate that FGP could be one of the fetal biomarkers and FGP-IM could be a premalignant lesion of intestinal type adenocarcinoma.We conducted another study to investigate the incidence of FGP-IM in gastric biopsy specimens and to identify FGP-IM as a predictor of the coexistence of accessory carcinoma and/or metachronous carcinoma. Eight endoscopic biopsy specimens of methylene blue-positive mucosa of the stomach were obtained from the patients with multiple gastric carcinomas (n=14), a single carcinoma (n=25) and atrophic gastritis (n=20), examined the incidence of FGP-IM. FGP positivity was 93.3% in the multiple carcinomas and 80.0% in the single carcinomas. The incidences of FGP-IM in the stomachs with multiple carcinomas, single carcinoma and atrophic gastritis were 83.2 ± 22.8%, 36.5 ± 41.3% and 7.1 ± 18.0%, respectively. The incidence of FGP-IM was significantly higher in the stomachs with multiple carcinomas than in those with a single carcinoma or atrophic gastritis. It is suggested that the frequent appearance of FGP-IM reflects the high potential of carcinogenesis of intestinal type gastric carcinoma and FGP-IM could be a predictive indicator of metachronous gastric carcinoma. Recently, there are increasing opportunities where endoscopic and laparoscopic local treatments are applied for the early gastric carcinoma, therefore, it is significantly important to identify the high-risk group of metachronous recurrence of gastric carcinoma. 2018Vol. and poorly ...

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Phosphorylase: A New Isozyme in Rat Hepatic Tumors and Fetal Liver

Cited by 58 publications

References 13 publications

Glycogen phosphorylase isoenzymes from hepatoma 3924A and from a non-tumorigenic liver cell line. Comparison with the liver and brain enzymes

Glycogen phosphorylase isoenzymes from hepatoma 3924A and from a non-tumorigenic liver cell line. Comparison with the liver and brain enzymes

Glycogenesis in the Cultured Fetal and Adult Rat Hepatocyte Is Differently Regulated by Medium Glucose

Fetal-type Glycogen Phosphorylase Expression in Intestinal Metaplasia as a Predictor of the Development of Gastric Cancer

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