Monastyrskaya E A, Andreeva L V, Duchen M R, Wiegant F, Bayda L A, Manukhina E B, Malyshev I Yu
Institute of General Pathology and Pathophysiology, Moscow, 125315, Russia.
Biochemistry (Mosc). 2003 Jul;68(7):816-21. doi: 10.1023/a:1025047303523.
Dosed adaptation to environmental factors is an efficient non-drug means for increasing the resistance of organs or the body as a whole. We demonstrated earlier that nitric oxide (NO) plays an important role in adaptive defense of the organism, in particular due to activation of heat shock protein (HSP) synthesis. A key question remained open--to what extent the formation of adaptive defense depends on central mechanisms and to what extent on the intracellular mechanisms immediately responding to the adapting factor, and whether the NO-dependent activation of HSP synthesis plays a role in adaptation of isolated cells. In the present study we looked into the possibility of producing a protective effect of adaptation to heat in cell culture. A 6-day adaptation to heat limited to 17% the decrease in metabolic activity induced by heat shock in H9c2 cardiomyoblasts. The development of adaptation was associated with increased NO production. Treatment of cells with the inhibitor of NO synthase L-NNA (100 micro M) prevented the development of adaptive protection. Adaptation of cell culture enhanced synthesis of HSP70 but not HSP27. Blockade of HSP70 synthesis with quercetin (50 micro M) left unchanged the protective effect of adaptation. Inhibition of NO synthesis restricted the adaptation-induced HSP70 synthesis. Therefore, the formation of adaptation at the cell level may result from a direct action of an environmental factor without participation of neuro-humoral factors. Such adaptation involves NO-dependent mechanisms divorced from the activation of HSP70 synthesis.
对环境因素的剂量适应性是增强器官或整个机体抵抗力的一种有效的非药物手段。我们之前已经证明，一氧化氮（NO）在机体的适应性防御中发挥重要作用，特别是由于热休克蛋白（HSP）合成的激活。一个关键问题仍然悬而未决——适应性防御的形成在多大程度上依赖于中枢机制，在多大程度上依赖于对适应因子立即做出反应的细胞内机制，以及NO依赖的HSP合成激活在分离细胞的适应过程中是否起作用。在本研究中，我们探讨了在细胞培养中产生热适应保护作用的可能性。对热进行6天的适应使H9c2心肌成纤维细胞中热休克诱导的代谢活性降低限制在17%。适应的发展与NO产生增加有关。用NO合酶抑制剂L-NNA（100微摩尔）处理细胞可阻止适应性保护的发展。细胞培养的适应增强了HSP70的合成，但未增强HSP27的合成。用槲皮素（50微摩尔）阻断HSP70合成并未改变适应的保护作用。抑制NO合成限制了适应诱导的HSP70合成。因此，细胞水平适应的形成可能是环境因素直接作用的结果，而无需神经体液因素的参与。这种适应涉及与HSP70合成激活无关的NO依赖机制。
