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人类肾透明细胞癌中的碳水化合物代谢

Carbohydrate metabolism in human renal clear cell carcinomas.

作者信息

Steinberg P, Störkel S, Oesch F, Thoenes W

机构信息

Institute of Toxicology, University of Mainz, Germany.

出版信息

Lab Invest. 1992 Oct;67(4):506-11.

PMID:1434530
Abstract

BACKGROUND

Renal cell carcinomas can be subclassified into clear cell carcinomas, chromophobe cell carcinomas, chromophilic cell carcinomas, and oncocytomas. Previous studies, in which no distinction among the different types of renal cell tumors and their grades of malignancy was performed, showed that these tumors had high glycolytic rates.

EXPERIMENTAL DESIGN

The carbohydrate metabolism of control human kidney samples and renal clear cell carcinomas with different degrees of cytologic malignancy (G I, G II, and G III) was studied by determining the glycogen and glucose-6-phosphate levels and the activities of key enzymes involved in glycolysis (hexokinase, glucokinase, pyruvate kinase), gluconeogenesis (glucose-6-phosphatase, fructose-1,6-diphosphatase), and the pentose phosphate pathway (glucose-6-phosphate dehydrogenase) in these tissues and compared with those of a limited number of chromophilic cell carcinomas, chromophobe cell carcinomas, and oncocytomas.

RESULTS

The glycogen and glucose-6-phosphate levels were significantly higher in G I, G II, and G III clear cut carcinomas than in control kidneys; glucokinase, hexokinase, and glucose-6-phosphate dehydrogenase activities remained unchanged, pyruvate kinase activity was enhanced, and glucose-6-phosphatase as well as fructose-1,6-diphosphatase activities were strongly reduced when compared with control kidney values. In chromophilic cell carcinomas glycogen content, glucose-6-phosphate dehydrogenase, and pyruvate kinase activities were elevated, while fructose-1,6-diphosphatase activity was reduced. In chromophobe cell carcinomas glycogen content was elevated and gluconeogenesis was reduced, whereas glycolysis was not activated. In oncocytomas glycogen was not detected and glucose-6-phosphate dehydrogenase, pyruvate kinase, and fructose-1,6-diphosphatase activities remained unchanged.

CONCLUSIONS

It has been demonstrated that a series of characteristic changes occur in the carbohydrate metabolism of renal clear cell carcinomas: glycogen and glucose-6-phosphate levels increase, glycolysis is activated, and gluconeogenesis is reduced. Furthermore, the alterations of the carbohydrate metabolism within clear cell carcinomas are clearly distinct from those observed in chromophilic cell carcinomas, chromophobe cell carcinomas, and oncocytomas.

摘要

背景

肾细胞癌可细分为透明细胞癌、嫌色细胞癌、嗜色细胞癌和嗜酸细胞瘤。以往的研究未对不同类型的肾细胞肿瘤及其恶性程度进行区分,结果显示这些肿瘤具有较高的糖酵解速率。

实验设计

通过测定对照人肾样本以及不同细胞学恶性程度(G I、G II和G III)的肾透明细胞癌组织中的糖原和6-磷酸葡萄糖水平,以及参与糖酵解(己糖激酶、葡萄糖激酶、丙酮酸激酶)、糖异生(6-磷酸葡萄糖磷酸酶、果糖-1,6-二磷酸酶)和磷酸戊糖途径(6-磷酸葡萄糖脱氢酶)的关键酶活性,研究其碳水化合物代谢情况,并与少量嗜色细胞癌、嫌色细胞癌和嗜酸细胞瘤的相应指标进行比较。

结果

与对照肾相比,G I、G II和G III级透明细胞癌中的糖原和6-磷酸葡萄糖水平显著升高;葡萄糖激酶、己糖激酶和6-磷酸葡萄糖脱氢酶活性保持不变,丙酮酸激酶活性增强,而6-磷酸葡萄糖磷酸酶以及果糖-1,6-二磷酸酶活性显著降低。在嗜色细胞癌中,糖原含量、6-磷酸葡萄糖脱氢酶和丙酮酸激酶活性升高,而果糖-1,6-二磷酸酶活性降低。在嫌色细胞癌中,糖原含量升高且糖异生减少,而糖酵解未被激活。在嗜酸细胞瘤中未检测到糖原,6-磷酸葡萄糖脱氢酶、丙酮酸激酶和果糖-1,6-二磷酸酶活性保持不变。

结论

已证明肾透明细胞癌的碳水化合物代谢发生了一系列特征性变化:糖原和6-磷酸葡萄糖水平升高,糖酵解被激活,糖异生减少。此外,透明细胞癌内碳水化合物代谢的改变与嗜色细胞癌、嫌色细胞癌和嗜酸细胞瘤中观察到的变化明显不同。

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