Self-aggregation of purified and membrane-bound erythrocyte CD38 induces extensive decrease of its ADP-ribosyl cyclase activity.
The transmembrane glycoprotein CD38 is a bifunctional enzyme that catalyzes at its ectocellular domain both the synthesis and the hydrolysis of cyclic ADP-ribose (cADPR). The complete reaction, converting NAD+ to nicotinamide and ADP-ribose, reproduces an NAD+glycohydrolase (NADase) reaction. CD38 purified from human erythrocyte membranes has been recently shown to undergo stable oligomerization induced by either NAD+ or beta-mercaptoethanol. We demonstrate that oligomerization is also triggered by reduced glutathione (GSH) and that the GSH-induced self-aggregation of purified CD38 is accompanied by extensive and comparable decrease of its ADP-ribosyl cyclase and NADase activities. GSH-induced oligomerization of CD38 and strong enzyme inactivation take place also in situ on erythrocyte membranes.
Institute of Biochemistry, University of Genoa, Italy.
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Zocchi
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Franco
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Guida
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Calder
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De Flora
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood* / Q000737:chemistry; D004910:Erythrocyte Membrane / Q000276:immunology*; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008623:Mercaptoethanol / Q000494:pharmacology; D009699:N-Glycosyl Hydrolases / Q000097:blood*; D009243:NAD / Q000378:metabolism / Q000494:pharmacology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D008623:Mercaptoethanol; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D005978:Glutathione