Dual effects of lysophosphatidic acid on human airway smooth muscle cell proliferation and survival

Tracy L. Ediger, Myron Lee Toews

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Lysophosphatidic acid (LPA) is a phospholipid growth mediator found in serum at 2-20 μM. In many cell types, including human airway smooth muscle (HASM) cells, LPA-induced proliferation occurs at 10-100 μM LPA. At these concentrations LPA forms Ca2+ precipitates. The potential involvement of Ca2+ and Ca2+-LPA precipitates in LPA-induced HASM cell mitogenesis was investigated. In the absence of extracellular Ca2+, 10 and 30 μM LPA stimulated HASM cell mitogenesis. However, with 100 μM LPA in the absence of extracellular Ca2+, HASM cells exhibited a profound shape change and loss of viability, determined to be apoptosis by both DNA staining and assessment of cytosolic nucleosomal reactivity. A bioassay based on the adenosine 3′:5′-cyclic monophosphate response of C62B rat glioma cells was used to measure the bioactivity of LPA solutions prepared in Ca2+-free and Ca2+-containing medium. After 24 h, a 100 μM LPA solution in Ca2+-free medium contained markedly greater bioactivity than a 100 μM LPA solution made in Ca2+-containing medium. In summary, formation of Ca2+-LPA precipitates decreases the amount of biologically active LPA in solution, and high concentrations of bioactive LPA achieved in Ca2+-free but not in Ca2+-containing medium induce apoptosis of HASM cells.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1531
Issue number1-2
DOIs
StatePublished - Mar 30 2001

Fingerprint

Smooth Muscle Myocytes
Cell Survival
Cell Proliferation
lysophosphatidic acid
Apoptosis
Glioma
Biological Assay
Adenosine
Phospholipids
Staining and Labeling

Keywords

  • Airway smooth muscle cell
  • Apoptosis
  • Extracellular Ca
  • Lysophosphatidic acid
  • Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

@article{2d98e61557e340ffb00978c108bc24e7,
title = "Dual effects of lysophosphatidic acid on human airway smooth muscle cell proliferation and survival",
abstract = "Lysophosphatidic acid (LPA) is a phospholipid growth mediator found in serum at 2-20 μM. In many cell types, including human airway smooth muscle (HASM) cells, LPA-induced proliferation occurs at 10-100 μM LPA. At these concentrations LPA forms Ca2+ precipitates. The potential involvement of Ca2+ and Ca2+-LPA precipitates in LPA-induced HASM cell mitogenesis was investigated. In the absence of extracellular Ca2+, 10 and 30 μM LPA stimulated HASM cell mitogenesis. However, with 100 μM LPA in the absence of extracellular Ca2+, HASM cells exhibited a profound shape change and loss of viability, determined to be apoptosis by both DNA staining and assessment of cytosolic nucleosomal reactivity. A bioassay based on the adenosine 3′:5′-cyclic monophosphate response of C62B rat glioma cells was used to measure the bioactivity of LPA solutions prepared in Ca2+-free and Ca2+-containing medium. After 24 h, a 100 μM LPA solution in Ca2+-free medium contained markedly greater bioactivity than a 100 μM LPA solution made in Ca2+-containing medium. In summary, formation of Ca2+-LPA precipitates decreases the amount of biologically active LPA in solution, and high concentrations of bioactive LPA achieved in Ca2+-free but not in Ca2+-containing medium induce apoptosis of HASM cells.",
keywords = "Airway smooth muscle cell, Apoptosis, Extracellular Ca, Lysophosphatidic acid, Proliferation",
author = "Ediger, {Tracy L.} and Toews, {Myron Lee}",
year = "2001",
month = "3",
day = "30",
doi = "10.1016/S1388-1981(01)00084-1",
language = "English (US)",
volume = "1531",
pages = "59--67",
journal = "Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids",
issn = "1388-1981",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Dual effects of lysophosphatidic acid on human airway smooth muscle cell proliferation and survival

AU - Ediger, Tracy L.

AU - Toews, Myron Lee

PY - 2001/3/30

Y1 - 2001/3/30

N2 - Lysophosphatidic acid (LPA) is a phospholipid growth mediator found in serum at 2-20 μM. In many cell types, including human airway smooth muscle (HASM) cells, LPA-induced proliferation occurs at 10-100 μM LPA. At these concentrations LPA forms Ca2+ precipitates. The potential involvement of Ca2+ and Ca2+-LPA precipitates in LPA-induced HASM cell mitogenesis was investigated. In the absence of extracellular Ca2+, 10 and 30 μM LPA stimulated HASM cell mitogenesis. However, with 100 μM LPA in the absence of extracellular Ca2+, HASM cells exhibited a profound shape change and loss of viability, determined to be apoptosis by both DNA staining and assessment of cytosolic nucleosomal reactivity. A bioassay based on the adenosine 3′:5′-cyclic monophosphate response of C62B rat glioma cells was used to measure the bioactivity of LPA solutions prepared in Ca2+-free and Ca2+-containing medium. After 24 h, a 100 μM LPA solution in Ca2+-free medium contained markedly greater bioactivity than a 100 μM LPA solution made in Ca2+-containing medium. In summary, formation of Ca2+-LPA precipitates decreases the amount of biologically active LPA in solution, and high concentrations of bioactive LPA achieved in Ca2+-free but not in Ca2+-containing medium induce apoptosis of HASM cells.

AB - Lysophosphatidic acid (LPA) is a phospholipid growth mediator found in serum at 2-20 μM. In many cell types, including human airway smooth muscle (HASM) cells, LPA-induced proliferation occurs at 10-100 μM LPA. At these concentrations LPA forms Ca2+ precipitates. The potential involvement of Ca2+ and Ca2+-LPA precipitates in LPA-induced HASM cell mitogenesis was investigated. In the absence of extracellular Ca2+, 10 and 30 μM LPA stimulated HASM cell mitogenesis. However, with 100 μM LPA in the absence of extracellular Ca2+, HASM cells exhibited a profound shape change and loss of viability, determined to be apoptosis by both DNA staining and assessment of cytosolic nucleosomal reactivity. A bioassay based on the adenosine 3′:5′-cyclic monophosphate response of C62B rat glioma cells was used to measure the bioactivity of LPA solutions prepared in Ca2+-free and Ca2+-containing medium. After 24 h, a 100 μM LPA solution in Ca2+-free medium contained markedly greater bioactivity than a 100 μM LPA solution made in Ca2+-containing medium. In summary, formation of Ca2+-LPA precipitates decreases the amount of biologically active LPA in solution, and high concentrations of bioactive LPA achieved in Ca2+-free but not in Ca2+-containing medium induce apoptosis of HASM cells.

KW - Airway smooth muscle cell

KW - Apoptosis

KW - Extracellular Ca

KW - Lysophosphatidic acid

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=0035970777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035970777&partnerID=8YFLogxK

U2 - 10.1016/S1388-1981(01)00084-1

DO - 10.1016/S1388-1981(01)00084-1

M3 - Article

VL - 1531

SP - 59

EP - 67

JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

SN - 1388-1981

IS - 1-2

ER -