THIOLS AND DISULFIDES CAN AGGRAVATE PEROXYNITRITE-DEPENDENT INACTIVATION OF ALPHA(1)-ANTIPROTEINASE

Peroxynitrite (ONOO-) is a cytotoxic species formed in vivo, There is considerable interest in the development of ONOO- 'scavengers' as ther apeutic agents; several thiols have been suggested to fulfil this role , One protein inactivated by ONOO- is alpha(1)-antiproteinase (alpha(1 )AP), the major inhibitor of serine proteinases in human body fluids, At low thiol:ONOO- concentration ratios, several thiols (captopril, pe nicillamine, cysteine, cystine and penicillamine disulphide) aggravate d inactivation of alpha(1)AP by ONOO-, whereas GSH, GSSG, homocysteine , ergothioneine, N-acetylcysteine, lipoate and dihydrolipoate did not, We suggest that sulphur-containing radicals are produced by reaction of certain thiols/disulphides with ONOO- or ONOO--derived products and could mediate biological damage, including inactivation of alpha(1)AP . This must be considered in attempts to use thiols as 'peroxynitrite scavengers'. (C) 1997 Federation of European Biochemical Societies.