Biomaterial Database

Antirheumatic gold compounds and penicillamine enhance protein kinase C-mediated activation of the arachidonate-mobilizing phospholipase A2 in mouse macrophages. 1993

J Bondeson, and R Sundler

Department of Medical and Physiological Chemistry, Malmö General Hospital, Lund University, Sweden.

The effects of antirheumatic gold compounds and D-penicillamine on protein kinase C- and Ca(2+)-mediated activation of arachidonate mobilization and the formation of eicosanoids in mouse macrophages have been investigated. Auranofin (0.2-2 microM) enhanced the response to phorbol ester two- to three-fold, and similar enhancement was caused by aurothiomalate, aurothioglucose, and penicillamine, but only after pretreatment for 1-4 h. The enhanced mobilization of arachidonate was accompanied by increased formation and release of prostaglandin E2 and 6-keto prostaglandin F1 alpha, but not of lipoxygenase metabolites. No such enhancement occurred when the arachidonate-mobilizing phospholipase A2 was activated directly (calcium ionophore A23187). Instead, auranofin caused selective inhibition of calcium ionophore-induced formation of leukotriene C4. Treatment of macrophages with 4 beta-phorbol 12-myristate 13-acetate causes a rapid increase in the phosphorylation and a 1.4-1.8-fold increase in the activity of the 85-kd arachidonate-mobilizing phospholipase A2 as determined in an in vitro assay. The increase in activity was further enhanced by both the gold compounds and penicillamine. These findings indicate that the target for the enhancing effect of the antirheumatic drugs is located between protein kinase C and phospholipase A2 in the signal chain leading to activation of the latter enzyme.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D010396	Penicillamine	3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.	Dimethylcysteine,Mercaptovaline,beta,beta-Dimethylcysteine,Copper Penicillaminate,Cuprenil,Cuprimine,D-3-Mercaptovaline,D-Penicillamine,Metalcaptase,D 3 Mercaptovaline,D Penicillamine,Penicillaminate, Copper,beta,beta Dimethylcysteine
D010741	Phospholipases A	Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D010750	Phosphoproteins		Phosphoprotein
D011494	Protein Kinases	A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.	Protein Kinase,Kinase, Protein,Kinases, Protein
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006051	Aurothioglucose	A thioglucose derivative used as an antirheumatic and experimentally to produce obesity in animals.	Gold Thioglucose,Aureotan,Auromyose,Aurothioglucose, Sodium Salt, beta-D Isomer,Aurothioglucose, beta-D Isomer,Gold-50,Solganal,Solganal B Oleosum,Solganol,Thioglucosoaurate,Aurothioglucose, beta D Isomer,B Oleosum, Solganal,Gold 50,Gold50,Oleosum, Solganal B,Thioglucose, Gold,beta-D Isomer Aurothioglucose
D006052	Gold Sodium Thiomalate	A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.	Aurothiomalate,Gold Thiomalate,Sodium Gold Thiomalate,Aurolate,Gold Disodium Thiomalate, Monohydrate,Gold Thiomalic Acid,Mercaptobutanedioic Acid Monogold(1+) Sodium Salt,Miocrin,Miocrisin,Monogold (1+) Disodium Thiomalate,Myochrysine,Myocrisin,Myocrysine,Sodium Aurothiomalate,Sodium Thiomalatoaurate,Tauredon,Aurothiomalate, Sodium,Gold Thiomalate, Sodium,Sodium Thiomalate, Gold,Thiomalate, Gold,Thiomalatoaurate, Sodium
D000001	Calcimycin	An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.	4-Benzoxazolecarboxylic acid, 5-(methylamino)-2-((3,9,11-trimethyl-8-(1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl)-1,7-dioxaspiro(5.5)undec-2-yl)methyl)-, (6S-(6alpha(2S,3S),8beta(R*),9beta,11alpha))-,A-23187,A23187,Antibiotic A23187,A 23187,A23187, Antibiotic