Cross-talk of NO, superoxide and molecular oxygen, a majesty of aerobic life

Because nitric oxide (NO) reacts with various molecules, such as hemeprotei ns, superoxide and thiols including glutathione (GSH) and cysteine residues in proteins, biological effects and metabolic fate of this gaseous radical are affected by these reactants. Although the lifetime of NO is short part icularly under air atmospheric conditions (where the oxygen tension is unph ysiologically high), it increases significantly under physiologically low o xygen concentrations. Because oxygen tensions in human body differ from one tissue to another and change depending on their metabolism, bioloical acti vity of NO in various tissues might be affected by local oxygen tensions. T o elucidate the role of NO and related radicals in the regulation of circul ation and energy metabolism, their effects on arterial resistance and energ y metabolism in mitochondria, mammalian cells and enteric bacteria were stu died under different oxygen tensions. Kinetic analysis revealed that NO-dep endent generation of cGMP in resistance arteries and their relaxation were strongly enhanced by lowering oxygen tensions in the medium. NO reversibly suppressed the respiration and ATP synthesis of isolated mitochondria and i ntact cells particularly under low oxygen tensions. Kinetic analysis reveal ed that cross-talk between NO and superoxide generated in and around endoth elial cells regulates arterial resistance particularly under physiologicall y low oxygen tensions. NO also inhibited the respiration and ATP synthesis of E, coli particularly under low oxygen tensions. Because concentrations o f NO and H+ in gastric juice are high, most ingested bacteria are effective ly killed in the stomach. However, the inhibitory effects of NO on the resp iration and ATP synthesis of H. pylori are extremely small. Kinetic analysi s revealed that H. pylori generates the superoxide radical thereby inhibiti ng the bactericidal action of NO in gastric juice. Based on such observatio ns, critical roles of the cross-talk of NO, superoxide and molecular oxygen in the regulation of energy metabolism and survival of aerobic and microae rophilic organisms are discussed.