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癌症患者分离出的红细胞中钠泵及钠/氢反向转运体功能受损。

Impairment of sodium pump and Na+/H+ antiport in erythrocytes isolated from cancer patients.

作者信息

Borg A L, Gallice P M, Kovacic H N, Nicoara A E, Favre R G, Crevat A D

机构信息

Biophysics Laboratory, Faculty of Pharmacy, Université d'Aix-Marseille II, France.

出版信息

Cancer Res. 1996 Feb 1;56(3):511-4.

PMID:8564963
Abstract

We sought to determine whether the impairment of sodium pump activity and Na+/H+ exchange reported in tumorigenic cells was specific to these cells or more general. Sodium pump activity and Na+/H+ exchange were measured in erythrocytes from 49 cancer patients and 51 healthy subjects. Cancer patients with a newly detected cancer or in relapse and without associated pathologies known to modify these sodium transporters were included in this study. Two sodium pump statuses reflecting its physiological modulation were evidenced for healthy subjects (10.3 +/- 0.2 and 19.4 +/- 0.8 mW/liter of cells). In cancer patients, only one basal status lower than those of controls was observed (8.3 +/- 0.5 mW/liter of cells; P < 0.001). Cooperativity of the Na+/H+ antiporter is the same in cancer patients and controls (2.58 +/- 0.27 versus 2.60 +/- 0.15). The intracellular pH (pHi) dependence curve of the antiporter was shifted toward more acidic values, and optimal pH1 was lower in cancer patients than in controls (5.80 +/- 0.03 versus 6.08 +/- 0.02; P < 0.0001). The mean maximal rate and the Km of H+ for the Na+/H+ antiporter were higher: 8.4 +/- 1.2 versus 4.6 +/- 0.4 mmol H+/liter of cells/h (P < 0.01) and 514 +/- 12 versus 322 +/- 16 nM (P < 0.05), respectively. Alterations of these Na+ transporters, therefore, were not restricted to cancerous cells. Among the alterations, the acidic shift in the pHi dependence of Na+/H+ exchange appears associated with cancer because this behavior has never been reported in other pathologies.

摘要

我们试图确定致瘤细胞中报道的钠泵活性和Na⁺/H⁺交换受损是这些细胞特有的,还是更具普遍性。我们测量了49例癌症患者和51名健康受试者红细胞中的钠泵活性和Na⁺/H⁺交换。本研究纳入了新检测出癌症或复发且无已知会改变这些钠转运蛋白的相关病理状况的癌症患者。健康受试者呈现出反映其生理调节的两种钠泵状态(10.3±0.2和19.4±0.8毫瓦/升细胞)。在癌症患者中,仅观察到一种低于对照组的基础状态(8.3±0.5毫瓦/升细胞;P<0.001)。癌症患者和对照组中Na⁺/H⁺反向转运体的协同性相同(2.58±0.27对2.60±0.15)。反向转运体的细胞内pH(pHi)依赖性曲线向更酸性值偏移,癌症患者的最佳pH1低于对照组(5.80±0.03对6.08±0.02;P<0.0001)。Na⁺/H⁺反向转运体的平均最大速率和H⁺的Km更高:分别为8.4±1.2对4.6±0.4毫摩尔H⁺/升细胞/小时(P<0.01)和514±12对322±16纳摩尔(P<0.05)。因此,这些Na⁺转运蛋白的改变并不局限于癌细胞。在这些改变中,Na⁺/H⁺交换的pHi依赖性酸性偏移似乎与癌症相关,因为这种行为从未在其他病理状况中报道过。

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