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Issue 887 coverMECHANISMS OF CELL DEATH: THE SECOND ANNUAL CONFERENCE OF THE CELL DEATH SOCIETY Copyright © 1999 by the New York Academy of Sciences
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Articles by BERNASSOLA, F.
Articles by MELINO, G.
Annals of the New York Academy of Sciences 887:83-91 (1999)
© 1999 New York Academy of Sciences

Regulation of Transglutaminases by Nitric Oxide

FRANCESCA BERNASSOLA, ANTONELLO ROSSI AND GERRY MELINOa

Biochemistry Laboratory, IDI-IRCCS, c/o Department of Experimental Medicine and Biochemical Science, University of Rome Tor Vergata, Rome, Italy

aCorresponding author: IDI-IRCCS, Biochemistry Lab, c/o Department of Experimental Medicine, D26/F153, University of Rome Tor Vergata, Via Tor Vergata 135, 00133 Rome, Italy. +39 6 20427299 (voice); + 39 6 20427290 (fax). e-mail: gerry.melino{at}uniroma2.it

Nitric oxide (NO) is an inorganic diffusible molecular messenger that plays several central roles in pathophysiology. NO can affect the biological activity of proteins through the direct or indirect (via intermeidate S-nitrosothiols) S-nitrosylation of protein thiol groups. Transglutaminases (TGases), CA++-dependent enzymes that modify proteins by cross-linking reactions, require a cysteine residue in the active site as a prerequisite for their catalytic activity. Therefore, NO may regulate enzymatic activity of TGases and their biological effects, via S-nitrosylation of their crucial thiol groups. We here review the effects of NO on coagulation factor XIII (fXIII, or plasma TGase) and Tgase 2 (or tissue transglutaminase). NO has an inhibitory effect on fXIII, thus suppressing the {gamma}-chain cross-linking in fibrin gels, and subsequent clot formation. Tissue transglutaminase, an apoptotic effector molecule, also represents a molecular target for NO. Accordingly, the inhibition of tissue transglutaminase enzymatic activity by NO is able to prevent the induction of apoptosis.

Abbreviations: bNO, nitric oxide • NOS, nitric oxide synthase • TGase, transglutaminase • tTG, tissue transglutaminase, fXIII, factor XIII • SNAP, S-nitroso-N-acetylpenicillamine • DTT, dithiothreitol • NMDA, N-methyl-d-aspartate.




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