Enhancement of endogenous production of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid in aortic smooth muscle cells by platelet-derived growth factor

Junko Nakao, Yasuko Koshihara, Hideki Ito, Sei Itsu Murota, Wen Chang Chang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Platelet-derived growth factor (PDGF) has a chemotactic effect on smooth muscle cells, which is inhibited by the lipoxygenase inhibitor caffeic acid. In order to study the role of endogenous lipoxygenase products of arachidonic acid on the chemotactic action of PDGF, effects of PDGF on the lipoxygenase pathway in smooth muscle cells were examined. Lipoxygenase products were analyzed by high-performance liquid chromatography. 15-, 5- and 12-lipoxygenase activities, in order of magnitude, were found in smooth muscle cell homogenate. However, when the lipoxygenase products were analyzed using intact cells prelabelled with [14C]arachidonic acid, only 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) was found to be produced endogenously. In addition, 12-HETE was not released into the medium. Treatment of the cells with PDGF increased the endogenous production of 12-HETE. The amounts of intracellular 12-HETE in PDGF-treated cells were 126, 132 and 146% at 1, 3, and 10 hr after the initiation of PDGF treatment, when the control value at each time point was considered as 100%. Caffeic acid (10-4 M) completely inhibited the PDGF effect on 12-HETE production. However, PDGF treatment did not significantly alter the 12-lipoxygenase activity. These results suggest that the stimulatory effect of PDGF on 12-HETE production was not mediated by the activation of 12-lipoxygenase activity. Since 12-HETE itself is a potent chemoattractant for smooth muscle cells, the present data strongly suggest that 12-HETE could be an important intracellular mediator of the chemotactic action of PDGF on aortic smooth muscle cells.

Original languageEnglish
Pages (from-to)1435-1442
Number of pages8
JournalLife Sciences
Volume37
Issue number15
DOIs
Publication statusPublished - 1985
Externally publishedYes

Fingerprint

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Arachidonic Acids
Platelet-Derived Growth Factor
Smooth Muscle Myocytes
Muscle
Cells
Lipoxygenase
Arachidonate 12-Lipoxygenase
Arachidonic Acid
Arachidonate Lipoxygenases
Arachidonate 5-Lipoxygenase
Lipoxygenase Inhibitors
Chemotactic Factors
High performance liquid chromatography
Chemical activation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Enhancement of endogenous production of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid in aortic smooth muscle cells by platelet-derived growth factor. / Nakao, Junko; Koshihara, Yasuko; Ito, Hideki; Murota, Sei Itsu; Chang, Wen Chang.

In: Life Sciences, Vol. 37, No. 15, 1985, p. 1435-1442.

Research output: Contribution to journalArticle

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abstract = "Platelet-derived growth factor (PDGF) has a chemotactic effect on smooth muscle cells, which is inhibited by the lipoxygenase inhibitor caffeic acid. In order to study the role of endogenous lipoxygenase products of arachidonic acid on the chemotactic action of PDGF, effects of PDGF on the lipoxygenase pathway in smooth muscle cells were examined. Lipoxygenase products were analyzed by high-performance liquid chromatography. 15-, 5- and 12-lipoxygenase activities, in order of magnitude, were found in smooth muscle cell homogenate. However, when the lipoxygenase products were analyzed using intact cells prelabelled with [14C]arachidonic acid, only 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) was found to be produced endogenously. In addition, 12-HETE was not released into the medium. Treatment of the cells with PDGF increased the endogenous production of 12-HETE. The amounts of intracellular 12-HETE in PDGF-treated cells were 126, 132 and 146{\%} at 1, 3, and 10 hr after the initiation of PDGF treatment, when the control value at each time point was considered as 100{\%}. Caffeic acid (10-4 M) completely inhibited the PDGF effect on 12-HETE production. However, PDGF treatment did not significantly alter the 12-lipoxygenase activity. These results suggest that the stimulatory effect of PDGF on 12-HETE production was not mediated by the activation of 12-lipoxygenase activity. Since 12-HETE itself is a potent chemoattractant for smooth muscle cells, the present data strongly suggest that 12-HETE could be an important intracellular mediator of the chemotactic action of PDGF on aortic smooth muscle cells.",
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AB - Platelet-derived growth factor (PDGF) has a chemotactic effect on smooth muscle cells, which is inhibited by the lipoxygenase inhibitor caffeic acid. In order to study the role of endogenous lipoxygenase products of arachidonic acid on the chemotactic action of PDGF, effects of PDGF on the lipoxygenase pathway in smooth muscle cells were examined. Lipoxygenase products were analyzed by high-performance liquid chromatography. 15-, 5- and 12-lipoxygenase activities, in order of magnitude, were found in smooth muscle cell homogenate. However, when the lipoxygenase products were analyzed using intact cells prelabelled with [14C]arachidonic acid, only 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) was found to be produced endogenously. In addition, 12-HETE was not released into the medium. Treatment of the cells with PDGF increased the endogenous production of 12-HETE. The amounts of intracellular 12-HETE in PDGF-treated cells were 126, 132 and 146% at 1, 3, and 10 hr after the initiation of PDGF treatment, when the control value at each time point was considered as 100%. Caffeic acid (10-4 M) completely inhibited the PDGF effect on 12-HETE production. However, PDGF treatment did not significantly alter the 12-lipoxygenase activity. These results suggest that the stimulatory effect of PDGF on 12-HETE production was not mediated by the activation of 12-lipoxygenase activity. Since 12-HETE itself is a potent chemoattractant for smooth muscle cells, the present data strongly suggest that 12-HETE could be an important intracellular mediator of the chemotactic action of PDGF on aortic smooth muscle cells.

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