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白藜芦醇处理诱导红细胞氧化还原应激:半胱天冬酶 3 在代谢和阴离子转运中的可能作用。

Resveratrol treatment induces redox stress in red blood cells: a possible role of caspase 3 in metabolism and anion transport.

机构信息

Department of Organic and Biological Chemistry, University of Messina, Salita Sperone 31, I-98166 Messina, Italy.

出版信息

Biol Chem. 2010 Sep;391(9):1057-65. doi: 10.1515/BC.2010.100.

DOI:10.1515/BC.2010.100
PMID:20536388
Abstract

Resveratrol, an important phytoalexine found in many plants, has been shown to be significantly effective in the treatment of several pathological conditions such as cancer, coronary heart disease and osteoarthritis. This study focuses on the effects of this drug on human red blood cells. In particular, we have examined the influence of resveratrol on Band 3, the anion exchanger protein, and hemoglobin as a function of the oxygenation-deoxygenation cycle. Moreover, special attention has been given to the metabolic changes imposed by caspase 3 activation. Resveratrol has proved to lower superoxide production, thereby decreasing heme-iron oxidation and saving the reducing power required for met-hemoglobin reduction. Oxygen binding experiments showed that resveratrol interacts with hemoglobin, shifting the T→R conformational transition towards the higher-affinity R state. This might contribute to altering the metabolic balance of the cell through an intensification of the pentose phosphate pathway. Moreover, at high oxygenation levels of the erythrocytic hemoglobin, resveratrol induces a significant activation of caspase 3, the action of which on Band 3 has a strong impact on cellular metabolism and anion transport.

摘要

白藜芦醇是一种在许多植物中发现的重要植物抗毒素,已被证明对多种病理状况(如癌症、冠心病和骨关节炎)的治疗具有显著效果。本研究专注于这种药物对人红细胞的影响。特别是,我们研究了白藜芦醇对阴离子交换蛋白 Band 3 和血红蛋白的影响,以及其作为氧合-去氧循环的功能。此外,还特别关注了半胱氨酸蛋白酶 3 激活所引起的代谢变化。白藜芦醇已被证明可降低超氧化物的产生,从而减少血红素铁的氧化,并节省用于高铁血红蛋白还原所需的还原能力。氧结合实验表明,白藜芦醇与血红蛋白相互作用,将 T→R 构象转变向更高亲和力的 R 状态移动。这可能有助于通过加强磷酸戊糖途径来改变细胞的代谢平衡。此外,在红细胞血红蛋白的高氧合水平下,白藜芦醇会诱导半胱氨酸蛋白酶 3 的显著激活,其对 Band 3 的作用对细胞代谢和阴离子转运有强烈影响。

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