Calabrese Vittorio, Stella A M Giuffrida, Butterfield D Allan, Scapagnini Giovanni
Section of Biochemistry and Molecular Biology, Department of Chemistry, Faculty of Medicine, University of Catania, Catania, Italy.
Antioxid Redox Signal. 2004 Oct;6(5):895-913. doi: 10.1089/ars.2004.6.895.
Efficient functioning of maintenance and repair processes seems to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of several genes termed "vitagenes," among these, the heat shock system, a highly conserved mechanism responsible for the preservation and repair of cellular macromolecules, such as proteins, RNAs, and DNA. Recent studies have shown that the heat shock response contributes to establishing a cytoprotective state in a wide variety of human diseases, including ischemia and reperfusion damage, inflammation, cancer, as well as metabolic and neurodegenerative disorders. Recently, the involvement of the heme oxygenase (HO) pathway in antidegenerative mechanisms has received considerable attention, as it has been demonstrated that the expression of HO is closely related to that of amyloid precursor protein. HO induction occurs together with the induction of other heat shock proteins during various physiopathological conditions. The vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, products of HO-catalyzed reaction, represent a protective system potentially active against brain oxidative injury. Given the broad cytoprotective properties of the heat shock response, molecules inducing this defense mechanism appear to be possible candidates for novel cytoprotective strategies. Particularly, manipulation of endogenous cellular defense mechanisms, via the heat shock response, through nutritional antioxidants or pharmacological compounds, may represent an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration. Consistently, by maintaining or recovering the activity of vitagenes, it is feasible to delay the aging process and decrease the occurrence of age-related diseases with resulting prolongation of a healthy life span.
维持和修复过程的有效运作对于生存和生活质量似乎都至关重要。这是通过一个由所谓的长寿保障过程组成的复杂网络来实现的，这些过程由几个被称为“维它基因”的基因组成，其中包括热休克系统，这是一种高度保守的机制，负责保存和修复细胞大分子，如蛋白质、RNA和DNA。最近的研究表明，热休克反应有助于在多种人类疾病中建立细胞保护状态，包括缺血再灌注损伤、炎症、癌症以及代谢和神经退行性疾病。最近，血红素加氧酶（HO）途径在抗退行性机制中的作用受到了相当大的关注，因为已经证明HO的表达与淀粉样前体蛋白的表达密切相关。在各种生理病理条件下，HO的诱导与其他热休克蛋白的诱导同时发生。血管活性分子一氧化碳和强效抗氧化剂胆红素是HO催化反应的产物，它们代表了一种可能对脑氧化损伤具有潜在活性的保护系统。鉴于热休克反应具有广泛的细胞保护特性，诱导这种防御机制的分子似乎是新型细胞保护策略的可能候选者。特别是，通过营养抗氧化剂或药物化合物，经由热休克反应来操纵内源性细胞防御机制，可能代表了一种针对导致组织损伤的疾病（如神经退行性变）进行治疗干预的创新方法。一致的是，通过维持或恢复维它基因的活性，延迟衰老过程并减少与年龄相关疾病的发生从而延长健康寿命是可行的。
