Cytochrome c, an ideal antioxidant.

Generation of DeltaPsi (membrane potential) by cytochrome oxidase proteoliposomes oxidizing superoxide-reduced cytochrome c has been demonstrated. XO+HX (xanthine oxidase and hypoxanthine) were used to produce superoxide. It was found that the generation of DeltaPsi is completely abolished by cyanide (an uncoupler) or by superoxide dismutase, and is enhanced by nigericin. Addition of ascorbate after XO+HX causes a further increase in DeltaPsi. On the other hand, XO+HX added after ascorbate do not affect DeltaPsi, indicating that superoxide does not have measurable protonophorous activity. The half-maximal cytochrome c concentration for DeltaPsi generation supported by XO+HX was found to be approx. 1 microM. These data and the results of some other researchers can be rationalized as follows: (1) O(2) accepts an electron to form superoxide; (2) cytochrome c oxidizes superoxide back to O(2); (3) an electron removed from the reduced cytochrome c is transferred to O(2) by cytochrome oxidase in a manner that generates Deltamicro(H(+)) (transmembrane difference in electrochemical H(+) potential). Thus cytochrome c mediates a process of superoxide removal, resulting in regeneration of O(2) and utilization of the electron involved previously in the O(2) reduction. It is important that cytochrome c is not damaged during the antioxidant reaction, in contrast with many other antioxidants.

The antioxidant functions of cytochrome c.

Low (C(1/2) = 1.5 x 10(-7) M) concentrations of horse cytochrome c strongly inhibit H(2)O(2) production by rat heart mitochondria under conditions of reverse electron transfer from succinate to NAD(+). The effect is abolished by binding of cytochrome c with liposomes and is not prevented by SOD. Yeast cytochrome c is much less effective than the horse protein whereas acetylated horse cytochrome c is without effect. H(2)O(2) formation stimulated by antimycin A is resistant to added cytochrome c. In inside-out submitochondrial vesicles, H(2)O(2) production is suppressed by all three cytochrome c samples tested, but at higher concentrations (C(1/2) is about 5 x 10(-7) M). In vesicles, SOD abolishes the cytochrome c inhibition. We conclude that extramitochondrial cytochrome c is competent in down-regulation of the Complex I H(2)O(2) production linked to the reverse electron transfer. Such an effect is absent in the inside-out submitochondrial vesicles where another antioxidant cytochrome c function can be observed, i.e. the oxidation of O(2-*) to O(2). A possible role of cytochrome c in the antioxidant defence is discussed.

[Pituitary adenylate cyclase activating peptide (PACAP)--its polyfunctionality in the mechanisms of brain protection]. / Peptid, aktiviruiushchii adenilattsiklazu gipofiza (PACAP)--polifunktsional'nost' v mekhanizmakh zashchity mozga.

Modern data of molecular and biological properties and physiological role of new pituitary adenylate cyclase activating polypeptide--PACAP--review. PACAP play key role in the embryogenesis of brain, in the protection of brain nerve cells from ischemia-induced death, injuring and apoptosis. New data are discussed concerned with molecular cloning and tissue distribution of receptors for PACAP, gene proPACAP expression in gastrointestinal tract, reproductive organs and nervous system. PACAP increase cytosolic free calcium and modifies the calcium-sensitive K(+)-channels, PACAP protects cultures cortical and hippocampal neurons from glutamate-induced cytotoxicity. The sleep modulation and modification of seizures activity of brain through the secretion of vasopressin or/and through NMDA receptors directly should be include in the program of PACAP "physiological continuum" of functions.