Phosphorylation-dependent stimulation of prostanoid synthesis by nigericin in cerebral endothelial cells

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Nigericin decreases intracellular pH (pH(i)) and stimulates prostanoid (PG) synthesis in endothelial cells from cerebral microvessels of newborn pigs. Nigericin-induced PG production was abolished by protein tyrosine kinase (PTK) inhibitors and amplified by phorbol 12-myristate 13-acetate (PMA) or protein tyrosine phosphatase (PTP) inhibitors. Nigericin-induced PG production in PMA-primed cells was potentiated by PTP inhibitors and abrogated by PTK inhibitors. Phospholipase A 2 (PLA 2) activity was stimulated by nigericin in a phosphorylation-dependent manner. Nigericin's effects on PG production and PLA 2 activity were reproduced by ionomycin, which activates cytosolic PLA 2 (cPLA 2). cPLA 2 was immunodetected in endothelial cell lysates. We found no evidence that nigericin's effects are mediated via mitogen-activated protein (MAP) kinase [extracellularly regulated kinase 1 (ERK1) and ERK2] activation: although nigericin stimulated detergentsoluble MAP kinase, its effects were not amplified by PMA or PTP inhibitors. Phosphorylation-dependent stimulation of PG synthesis was also observed when phi was decreased by sodium propionate or a high level of CO 2. Altogether, our data indicate that nigericin and decreased phi stimulate PG synthesis by a protein phosphorylation-dependent mechanism involving cross talk between pathways mediated by PTK and PTP and by protein kinase C; cPLA 2 appears to be a key enzyme affected by nigericin and decreased pH(i).

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume277
Issue number4 46-4
StatePublished - 1999

Fingerprint

Nigericin
Phosphorylation
Endothelial cells
Prostaglandins
Endothelial Cells
Protein Tyrosine Phosphatases
Protein-Tyrosine Kinases
Phospholipases A
Acetates
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Ionomycin
Carbon Monoxide
Microvessels
Protein Kinase C
Phosphotransferases
Swine
Chemical activation

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

@article{169ff081161041d4ae34563dca5b6a55,
title = "Phosphorylation-dependent stimulation of prostanoid synthesis by nigericin in cerebral endothelial cells",
abstract = "Nigericin decreases intracellular pH (pH(i)) and stimulates prostanoid (PG) synthesis in endothelial cells from cerebral microvessels of newborn pigs. Nigericin-induced PG production was abolished by protein tyrosine kinase (PTK) inhibitors and amplified by phorbol 12-myristate 13-acetate (PMA) or protein tyrosine phosphatase (PTP) inhibitors. Nigericin-induced PG production in PMA-primed cells was potentiated by PTP inhibitors and abrogated by PTK inhibitors. Phospholipase A 2 (PLA 2) activity was stimulated by nigericin in a phosphorylation-dependent manner. Nigericin's effects on PG production and PLA 2 activity were reproduced by ionomycin, which activates cytosolic PLA 2 (cPLA 2). cPLA 2 was immunodetected in endothelial cell lysates. We found no evidence that nigericin's effects are mediated via mitogen-activated protein (MAP) kinase [extracellularly regulated kinase 1 (ERK1) and ERK2] activation: although nigericin stimulated detergentsoluble MAP kinase, its effects were not amplified by PMA or PTP inhibitors. Phosphorylation-dependent stimulation of PG synthesis was also observed when phi was decreased by sodium propionate or a high level of CO 2. Altogether, our data indicate that nigericin and decreased phi stimulate PG synthesis by a protein phosphorylation-dependent mechanism involving cross talk between pathways mediated by PTK and PTP and by protein kinase C; cPLA 2 appears to be a key enzyme affected by nigericin and decreased pH(i).",
author = "Elena Parfenova and John Haffner and Charles Leffler",
year = "1999",
language = "English (US)",
volume = "277",
journal = "American Journal of Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "4 46-4",

}

TY - JOUR

T1 - Phosphorylation-dependent stimulation of prostanoid synthesis by nigericin in cerebral endothelial cells

AU - Parfenova, Elena

AU - Haffner, John

AU - Leffler, Charles

PY - 1999

Y1 - 1999

N2 - Nigericin decreases intracellular pH (pH(i)) and stimulates prostanoid (PG) synthesis in endothelial cells from cerebral microvessels of newborn pigs. Nigericin-induced PG production was abolished by protein tyrosine kinase (PTK) inhibitors and amplified by phorbol 12-myristate 13-acetate (PMA) or protein tyrosine phosphatase (PTP) inhibitors. Nigericin-induced PG production in PMA-primed cells was potentiated by PTP inhibitors and abrogated by PTK inhibitors. Phospholipase A 2 (PLA 2) activity was stimulated by nigericin in a phosphorylation-dependent manner. Nigericin's effects on PG production and PLA 2 activity were reproduced by ionomycin, which activates cytosolic PLA 2 (cPLA 2). cPLA 2 was immunodetected in endothelial cell lysates. We found no evidence that nigericin's effects are mediated via mitogen-activated protein (MAP) kinase [extracellularly regulated kinase 1 (ERK1) and ERK2] activation: although nigericin stimulated detergentsoluble MAP kinase, its effects were not amplified by PMA or PTP inhibitors. Phosphorylation-dependent stimulation of PG synthesis was also observed when phi was decreased by sodium propionate or a high level of CO 2. Altogether, our data indicate that nigericin and decreased phi stimulate PG synthesis by a protein phosphorylation-dependent mechanism involving cross talk between pathways mediated by PTK and PTP and by protein kinase C; cPLA 2 appears to be a key enzyme affected by nigericin and decreased pH(i).

AB - Nigericin decreases intracellular pH (pH(i)) and stimulates prostanoid (PG) synthesis in endothelial cells from cerebral microvessels of newborn pigs. Nigericin-induced PG production was abolished by protein tyrosine kinase (PTK) inhibitors and amplified by phorbol 12-myristate 13-acetate (PMA) or protein tyrosine phosphatase (PTP) inhibitors. Nigericin-induced PG production in PMA-primed cells was potentiated by PTP inhibitors and abrogated by PTK inhibitors. Phospholipase A 2 (PLA 2) activity was stimulated by nigericin in a phosphorylation-dependent manner. Nigericin's effects on PG production and PLA 2 activity were reproduced by ionomycin, which activates cytosolic PLA 2 (cPLA 2). cPLA 2 was immunodetected in endothelial cell lysates. We found no evidence that nigericin's effects are mediated via mitogen-activated protein (MAP) kinase [extracellularly regulated kinase 1 (ERK1) and ERK2] activation: although nigericin stimulated detergentsoluble MAP kinase, its effects were not amplified by PMA or PTP inhibitors. Phosphorylation-dependent stimulation of PG synthesis was also observed when phi was decreased by sodium propionate or a high level of CO 2. Altogether, our data indicate that nigericin and decreased phi stimulate PG synthesis by a protein phosphorylation-dependent mechanism involving cross talk between pathways mediated by PTK and PTP and by protein kinase C; cPLA 2 appears to be a key enzyme affected by nigericin and decreased pH(i).

UR - http://www.scopus.com/inward/record.url?scp=0032743181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032743181&partnerID=8YFLogxK

M3 - Article

C2 - 10516103

AN - SCOPUS:0032743181

VL - 277

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1931-857X

IS - 4 46-4

ER -