A pyrrolidine-based specific inhibitor of cytosolic phospholipase A2α blocks arachidonic acid release in a variety of mammalian cells

被引：86

作者：

Ghomashchi, F

Stewart, A

Hefner, Y

Ramanadham, S

Turk, J

Leslie, CC

Gelb, MH ^{[1
]}

机构：

[1] Univ Washington, Dept Chem, Seattle, WA 98195 USA

[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[3] Natl Jewish Med & Res Ctr, Cell Biol Program, Dept Pediat, Denver, CO 80206 USA

[4] Washington Univ, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, St Louis, MO 63110 USA

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2001年 / 1513卷 / 02期

关键词：

cystolic phospholipase; arachidonic acid; pyrrolidine-based inhibitor;

D O I：

10.1016/S0005-2736(01)00349-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We analyzed a recently reported (K. Seno, T. Okuno. K. Nishi. Y. Murakami, F. Watanabe., T. Matsuur, M. Wada, Y. Fujii, M. Yamada. T. Ogawa. T. Okada. H, Hashizume, M. Kii, S.-H. Hara, S. Hagishita, S. Nakamoto, J. Med. Chem. 43 (2000)) pyrrolidine-based inhibitor, pyrrolidine-1, against the human group IV cytosolic phospholipase A(2) alpha -isoform (cPLA(2)alpha). Pyrrolidine-1 inhibits cPLA(2)alpha by 50% when present at approx. 0.002 mole fraction in the interface in a number of in vitro assays. It is much less potent on the cPLA(2)gamma isoform, calcium-independent group VI PLA, and groups IIA, X, and V secreted PLA(2)s, Pyrrolidine-1 blocked all of the arachidonic acid released in Ca2+ ionophore-stimulated CHO cells stably transfected with cPLA(2 alpha), in zymosan- and okadaic acid-stimulated mouse peritoneal macrophages, and in ATP- and Ca2+ ionophore-stimulated MDCK cells. (C) 2001 Elsevier Science B.V. All rights reserved.

引用

页码：160 / 166

页数：7

共 45 条

[31] Secretory phospholipase A2 is the principal bactericide for staphylococci and other gram-positive bacteria in human tears [J].