2Semenov Institute of Chemical Physics, Russian Academy of Sciences, ul. Kosygina 4, 119334 Moscow, Russia; fax: (499) 137-4101; E-mail: firstname.lastname@example.org
* To whom correspondence should be addressed.
Received April 28, 2011; Revision received May 25, 2011
This review discusses the functional role of nitric oxide in ischemia–reperfusion injury and mechanisms of signal transduction of apoptosis, which accompanies ischemic damage to organs and tissues. On induction of apoptosis an interaction is observed of the nitric oxide signaling system with the sphingomyelin cycle, which is a source of a proapoptotic agent ceramide. Evidence is presented of an interaction of the sphingomyelin cycle enzymes and ceramide with nitric oxide and enzymes synthesizing nitric oxide. The role of a proinflammatory cytokine TNF-α in apoptosis and ischemia–reperfusion and mechanisms of its cytotoxic action, which involve nitric oxide, the sphingomyelin cycle, and lipid peroxidation are discussed. A comprehensive study of these signaling systems provides insight into the molecular mechanism of apoptosis during ischemia and allows us to consider new approaches for treatment of diseases associated with the activation of apoptosis.
KEY WORDS: nitric oxide, sphingomyelin cycle, ceramide, lipid peroxidation, tumor necrosis factor-α, apoptosis, ischemia–reperfusion