Antirheumatic gold compounds and penicillamine enhance protein kinase C-mediated activation of the arachidonate-mobilizing phospholipase A2 in mouse macrophages
(1993) In Journal of Leukocyte Biology 54(4). p.35-329- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/30110
- author
- Bondeson, J and Sundler, Roger LU
- organization
- publishing date
- 1993
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Leukocyte Biology
- volume
- 54
- issue
- 4
- pages
- 35 - 329
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:0027484756
- ISSN
- 1938-3673
- language
- English
- LU publication?
- yes
- id
- 63e76ef0-389b-4217-a621-4ada47f0a45e (old id 30110)
- date added to LUP
- 2016-04-01 12:19:20
- date last changed
- 2021-01-03 09:15:35
@article{63e76ef0-389b-4217-a621-4ada47f0a45e,
abstract = {{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.}},
author = {{Bondeson, J and Sundler, Roger}},
issn = {{1938-3673}},
language = {{eng}},
number = {{4}},
pages = {{35--329}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Leukocyte Biology}},
title = {{Antirheumatic gold compounds and penicillamine enhance protein kinase C-mediated activation of the arachidonate-mobilizing phospholipase A2 in mouse macrophages}},
volume = {{54}},
year = {{1993}},
}