Afanas'ev I B
Vitamin Research Institute, Nauchny pr.14A, Moscow 117820, Russia.
Med Hypotheses. 2005;64(1):127-9. doi: 10.1016/j.mehy.2004.05.009.
It has been demonstrated that in various physiological and pathophysiological processes superoxide functions as a signaling molecule by the way different from those mediated by hydrogen peroxide, hydroxyl radicals, or peroxynitrite. However, until now the mechanism of superoxide signaling remains obscure. A well known role of superoxide as a precursor of reactive hydroxyl radicals by the superoxide-dependent Fenton reaction or the formation of peroxynitrite must result in the damage of the target molecules and lead to pathological disorders. However, this mechanism is unlikely in such processes as the stimulation by superoxide of enzymatic phosphorylation and dephosphorylation. But, not being a "super-oxidant", superoxide possesses the frequently forgotten "super"-nucleophilic properties. Now, we propose a new mechanism for superoxide signaling depending on its nucleophilic reactions. Possible nucleophilic mechanisms of superoxide signaling in the hydrolysis of phosphatidylinositol to inositol 1,4,5-tris-phosphate and in the catalysis of phosphorylation by mitogen-activated protein kinases, phospholipase C and other enzymes are considered.
已经证明，在各种生理和病理生理过程中，超氧化物作为一种信号分子发挥作用，其方式不同于由过氧化氢、羟基自由基或过氧亚硝酸盐介导的方式。然而，迄今为止，超氧化物信号传导的机制仍然不清楚。超氧化物通过超氧化物依赖性芬顿反应作为活性羟基自由基的前体或形成过氧亚硝酸盐的众所周知的作用必然导致靶分子的损伤并导致病理紊乱。然而，在超氧化物刺激酶促磷酸化和去磷酸化等过程中，这种机制不太可能。但是，超氧化物并非“超氧化物”，它具有经常被遗忘的“超”亲核特性。现在，我们提出了一种基于其亲核反应的超氧化物信号传导新机制。考虑了超氧化物信号传导在磷脂酰肌醇水解为肌醇1,4,5-三磷酸以及在丝裂原活化蛋白激酶、磷脂酶C和其他酶催化的磷酸化中的可能亲核机制。
