The antiplatelet activity of PMC, a potent α-tocopherol analogue, is mediated through inhibition of cyclo-oxygenase

Joen R. Sheu, Cheng R. Lee, Chang C. Lin, Ya C. Kan, Chien-Huang Lin, Wei C. Hung, Yen M. Lee, Mao H. Yen

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

1. PMC, a potent α-tocopherol derivative, dose-dependently (5-25 μM) inhibited the ATP-release reaction and platelet aggregation in washed human platelets stimulated by agonists (collagen and ADP). 2. PMC also dose-dependently inhibited the intracellular Ca2+ mobilization, whereas it did not inhibit phosphoinositide breakdown in human platelets stimulated by collagen. 3. PMC (10 and 25 μM) significantly inhibited collagen-stimulated thromboxane A2 (TxA2) formation in human platelets. On the other hand, PMC (25 and 100 μM) did not increase the formation of cyclic AMP or cyclic GMP in platelets. Moreover, PMC (25, 100, and 200 μM) did not affect the thromboxane synthetase activity of aspirin-treated platelet microsomes. 4. PMC (10 and 25 μM) markedly inhibited the exogenous arachidonic acid (100 μM)-induced prostaglandin E2 (PGE2) formation in the presence of imidazole (600 μM) in washed human platelets, indicating that PMC inhibits cyclo-oxygenase activity. 5. We conclude that PMC may exert its anti-platelet aggregation activity by inhibiting cyclo-oxygenase activity, which leads to reduced prostaglandin formation; this, in turn, is followed by a reduction of TxA2 formation, and finally inhibition of [Ca2+](i) mobilization and ATP-release.

Original languageEnglish
Pages (from-to)1206-1212
Number of pages7
JournalBritish Journal of Pharmacology
Volume127
Issue number5
DOIs
Publication statusPublished - 1999

Fingerprint

Tocopherols
Prostaglandin-Endoperoxide Synthases
Blood Platelets
Thromboxane A2
Collagen
Platelet Aggregation
Adenosine Triphosphate
Thromboxane-A Synthase
Cyclic GMP
Microsomes
Phosphatidylinositols
Dinoprostone
Arachidonic Acid
Cyclic AMP
Adenosine Diphosphate
Aspirin
Prostaglandins

Keywords

  • α-tocopherol
  • Cyclo-oxygenase
  • Platelet aggregation
  • PMC

ASJC Scopus subject areas

  • Pharmacology

Cite this

The antiplatelet activity of PMC, a potent α-tocopherol analogue, is mediated through inhibition of cyclo-oxygenase. / Sheu, Joen R.; Lee, Cheng R.; Lin, Chang C.; Kan, Ya C.; Lin, Chien-Huang; Hung, Wei C.; Lee, Yen M.; Yen, Mao H.

In: British Journal of Pharmacology, Vol. 127, No. 5, 1999, p. 1206-1212.

Research output: Contribution to journalArticle

Sheu, Joen R. ; Lee, Cheng R. ; Lin, Chang C. ; Kan, Ya C. ; Lin, Chien-Huang ; Hung, Wei C. ; Lee, Yen M. ; Yen, Mao H. / The antiplatelet activity of PMC, a potent α-tocopherol analogue, is mediated through inhibition of cyclo-oxygenase. In: British Journal of Pharmacology. 1999 ; Vol. 127, No. 5. pp. 1206-1212.
@article{86e32754ef4c4782b4eecb320944176f,
title = "The antiplatelet activity of PMC, a potent α-tocopherol analogue, is mediated through inhibition of cyclo-oxygenase",
abstract = "1. PMC, a potent α-tocopherol derivative, dose-dependently (5-25 μM) inhibited the ATP-release reaction and platelet aggregation in washed human platelets stimulated by agonists (collagen and ADP). 2. PMC also dose-dependently inhibited the intracellular Ca2+ mobilization, whereas it did not inhibit phosphoinositide breakdown in human platelets stimulated by collagen. 3. PMC (10 and 25 μM) significantly inhibited collagen-stimulated thromboxane A2 (TxA2) formation in human platelets. On the other hand, PMC (25 and 100 μM) did not increase the formation of cyclic AMP or cyclic GMP in platelets. Moreover, PMC (25, 100, and 200 μM) did not affect the thromboxane synthetase activity of aspirin-treated platelet microsomes. 4. PMC (10 and 25 μM) markedly inhibited the exogenous arachidonic acid (100 μM)-induced prostaglandin E2 (PGE2) formation in the presence of imidazole (600 μM) in washed human platelets, indicating that PMC inhibits cyclo-oxygenase activity. 5. We conclude that PMC may exert its anti-platelet aggregation activity by inhibiting cyclo-oxygenase activity, which leads to reduced prostaglandin formation; this, in turn, is followed by a reduction of TxA2 formation, and finally inhibition of [Ca2+](i) mobilization and ATP-release.",
keywords = "α-tocopherol, Cyclo-oxygenase, Platelet aggregation, PMC",
author = "Sheu, {Joen R.} and Lee, {Cheng R.} and Lin, {Chang C.} and Kan, {Ya C.} and Chien-Huang Lin and Hung, {Wei C.} and Lee, {Yen M.} and Yen, {Mao H.}",
year = "1999",
doi = "10.1038/sj.bjp.0702637",
language = "English",
volume = "127",
pages = "1206--1212",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - The antiplatelet activity of PMC, a potent α-tocopherol analogue, is mediated through inhibition of cyclo-oxygenase

AU - Sheu, Joen R.

AU - Lee, Cheng R.

AU - Lin, Chang C.

AU - Kan, Ya C.

AU - Lin, Chien-Huang

AU - Hung, Wei C.

AU - Lee, Yen M.

AU - Yen, Mao H.

PY - 1999

Y1 - 1999

N2 - 1. PMC, a potent α-tocopherol derivative, dose-dependently (5-25 μM) inhibited the ATP-release reaction and platelet aggregation in washed human platelets stimulated by agonists (collagen and ADP). 2. PMC also dose-dependently inhibited the intracellular Ca2+ mobilization, whereas it did not inhibit phosphoinositide breakdown in human platelets stimulated by collagen. 3. PMC (10 and 25 μM) significantly inhibited collagen-stimulated thromboxane A2 (TxA2) formation in human platelets. On the other hand, PMC (25 and 100 μM) did not increase the formation of cyclic AMP or cyclic GMP in platelets. Moreover, PMC (25, 100, and 200 μM) did not affect the thromboxane synthetase activity of aspirin-treated platelet microsomes. 4. PMC (10 and 25 μM) markedly inhibited the exogenous arachidonic acid (100 μM)-induced prostaglandin E2 (PGE2) formation in the presence of imidazole (600 μM) in washed human platelets, indicating that PMC inhibits cyclo-oxygenase activity. 5. We conclude that PMC may exert its anti-platelet aggregation activity by inhibiting cyclo-oxygenase activity, which leads to reduced prostaglandin formation; this, in turn, is followed by a reduction of TxA2 formation, and finally inhibition of [Ca2+](i) mobilization and ATP-release.

AB - 1. PMC, a potent α-tocopherol derivative, dose-dependently (5-25 μM) inhibited the ATP-release reaction and platelet aggregation in washed human platelets stimulated by agonists (collagen and ADP). 2. PMC also dose-dependently inhibited the intracellular Ca2+ mobilization, whereas it did not inhibit phosphoinositide breakdown in human platelets stimulated by collagen. 3. PMC (10 and 25 μM) significantly inhibited collagen-stimulated thromboxane A2 (TxA2) formation in human platelets. On the other hand, PMC (25 and 100 μM) did not increase the formation of cyclic AMP or cyclic GMP in platelets. Moreover, PMC (25, 100, and 200 μM) did not affect the thromboxane synthetase activity of aspirin-treated platelet microsomes. 4. PMC (10 and 25 μM) markedly inhibited the exogenous arachidonic acid (100 μM)-induced prostaglandin E2 (PGE2) formation in the presence of imidazole (600 μM) in washed human platelets, indicating that PMC inhibits cyclo-oxygenase activity. 5. We conclude that PMC may exert its anti-platelet aggregation activity by inhibiting cyclo-oxygenase activity, which leads to reduced prostaglandin formation; this, in turn, is followed by a reduction of TxA2 formation, and finally inhibition of [Ca2+](i) mobilization and ATP-release.

KW - α-tocopherol

KW - Cyclo-oxygenase

KW - Platelet aggregation

KW - PMC

UR - http://www.scopus.com/inward/record.url?scp=0032795923&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032795923&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0702637

DO - 10.1038/sj.bjp.0702637

M3 - Article

C2 - 10455267

AN - SCOPUS:0032795923

VL - 127

SP - 1206

EP - 1212

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 5

ER -