VITAMINS

As to the vitamin C activity of DAsA in humans, L-ascorbic acid (AsA) and dehydro-L-ascorbic acid (DAsA) have been reported to have equal vitamin C activity, according to the Vitamin C Research Group of the Vitamin Society of Japan since the fourth revised edition (1982) of the Standard Tables of Food Composition in Japan. In the present study, tests on growth and recovery by oral administration of various levels of DAsA and AsA to ODS rats were carried out. DAsA at the doses of 0.02 mmol/day or 0.03 mmol/day made ODS rats grew well, and even in the recovery test after vitamin C-deficiency feeding for 1 to 2 weeks, the DAsA administration group showed almost the same activity state as the AsA administration group. In each feeding test, the total vitamin C content in tissues of ODS rats in the AsA oral administration group was about 1.6〜2 times higher compared with that with the oral administration of DAsA. The data reported here suggest that the vitamin C effect of DAsA in ODS rats is less than that of AsA.

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Receptor stimulation and other cellular stimulations such as heat, osmotic stress and oxidative stress evoke activation of Ca^<2+> -permeable cation channels. Recent studies have demonstrated that molecular entities of these Ca^<2+> -permeable cation channels are formed by mammalian homologues of Drosophila transient receptor potential (TRP) proteins. We have identified that a widely expressed Ca^<2+> -permeable cation channel TRPM2 is activated by reactive oxygen or nitrogen species-generating agents including H_2O_2 of micromolar levels. This sensitivity of TRPM2 to redox state modifiers was attributable to an agonistic binding of nicotinamide adenine dinucleotide (β-NAD^+) to the MutT, a nucleotide binding motif. In native and heterologous expression system, TRPM2 was involved in H_2O_2 - induced Ca^<2+> influx and cell death. Thus, TRPM2 represents an important intrinsic mechanism that mediates Ca^<2+> and Na^+ overload in response to disturbance of redox state in cell death.

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Some 40 years has passed since poly(ADP-ribose) and the poly(ADP-ribosyl)ation reaction were discovered. Characteristics of poly(ADP-ribose) with a huge biopolymer with branching makes poly (ADP-ribosyl)ation a powerful post-translational modification of biological materials as well as a unique structural component of eukaryotic cell chromatin. Localization of poly(ADP-ribose) poly-merase (PARP-1) in the nucleus and its enzymatic activation by DNA strand break makes this modification an important mechanism of DNA repair and other reactions involved in DNA metabolism. However this reaction turned to be not confined in the nucleus but might be involved in the cytoplasmic events. Recent findings in our laboratory clarified that PARP-1 also localizes to the centrosome and the cells from knockout mice of PARP-1 shows several abnormalities related to the centrosome function. Involvement of poly(ADP-ribose) metabolism in regulation of neuronal cell function was also indicated. This review describes such recent findings suggesting the metabolism of poly(ADP- ribose) is very dynamic and important for maintenance of cell functions.

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NAD is involved in the numerous metabolic reactions as a major coenzyme. Further, NAD is known as the ADP-ribose donor for the covalent modifications (mono-and poly-ADP-ribosylation) or the synthesis of a signaling molecule, cyclic ADP-ribose. Mono-ADP-ribosylation is a posttranslational modification in which the ADP-ribose moiety of NAD is transferred to target amino acid residues in the proteins or peptides. Bacterial toxins, such as chorela and pertuissis, include mono-ADP-ribosyltransferase activity and modify the crucial cellular proteins Gsa and Gioc, thereby resulting in the disturbance of cellular function. Mono-ADP-ribosyltransferases have been detected not only in bacteria but also in eukaryotes, and vertebrate ADP-ribosyltransferases have been identified in various tissues and cells. In this review, we have highlighted and outlined the arginine-specific ADP-ribosyltransferases 'Arts' in vertebrates, and discussed the possible roles of Arts in cellular functions. We have also described newly identified chicken glycosylphosphatidylinositol (GPI)-anchored Arts. Vertebrate Arts, and ADP-ribosylarginine hydrolases which cleave ADP-ribose-arginine linkage on the protein, are constitutively expressed on cells and may play critical roles for various cellular functions via ADP-ribosylation and de-ADP-ribosylation cycle. Recent research developments in the ADP-ribosylation would disclose its involvement in cellular processes in the near future.

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