Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation

Jun Liu, Peiyee Lee, Ferruccio Galbiati, Richard N. Kitsis, Michael P. Lisanti

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

The potential role of caveolin-1 in apoptosis remains controversial. Here, we investigate whether caveolin-1 expression is proapoptotic or antiapoptotic using a well-defined antisense approach. We show that NIH/3T3 cells harboring antisense caveolin-1 are resistant to staurosporine-induced apoptosis, as assessed using cell morphology, DNA content, caspase 3 activation, and focal adhesion kinase cleavage. Importantly, sensitivity to apoptosis is recovered when caveolin-1 levels are restored. Conversely, recombinant stable expression of caveolin-1 in T24 bladder carcinoma cells sensitizes these cells to caspase 3 activation. Consistent with the observations using NIH/3T3 cells, downregulation of caveolin-1 in T24 cells substantially diminishes caspase 3-like activity. Loss of sensitivity to apoptotic stimulation is recovered by inhibition of the phosphatidylinositol 3-kinase pathway using LY-294002, suggesting a possible mechanism for the sensitizing effect of caveolin-1. Thus our results suggest that caveolin-1 may act as a coupling or sensitizing factor in signaling apoptotic cell death in both fibroblastic (NIH/3T3) and epithelial (T24) cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume280
Issue number4 49-4
StatePublished - 2001

Fingerprint

Caveolin 1
Epithelial Cells
Caspase 3
NIH 3T3 Cells
Apoptosis
Chemical activation
Phosphatidylinositol 3-Kinase
Focal Adhesion Protein-Tyrosine Kinases
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Staurosporine
Cell death
Urinary Bladder
Cell Death
Down-Regulation
Cells
Carcinoma
DNA

Keywords

  • Caveolae
  • Caveolin
  • Signaling

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation. / Liu, Jun; Lee, Peiyee; Galbiati, Ferruccio; Kitsis, Richard N.; Lisanti, Michael P.

In: American Journal of Physiology - Cell Physiology, Vol. 280, No. 4 49-4, 2001.

Research output: Contribution to journalArticle

@article{97901ab637d9413ea8817e696bb349b9,
title = "Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation",
abstract = "The potential role of caveolin-1 in apoptosis remains controversial. Here, we investigate whether caveolin-1 expression is proapoptotic or antiapoptotic using a well-defined antisense approach. We show that NIH/3T3 cells harboring antisense caveolin-1 are resistant to staurosporine-induced apoptosis, as assessed using cell morphology, DNA content, caspase 3 activation, and focal adhesion kinase cleavage. Importantly, sensitivity to apoptosis is recovered when caveolin-1 levels are restored. Conversely, recombinant stable expression of caveolin-1 in T24 bladder carcinoma cells sensitizes these cells to caspase 3 activation. Consistent with the observations using NIH/3T3 cells, downregulation of caveolin-1 in T24 cells substantially diminishes caspase 3-like activity. Loss of sensitivity to apoptotic stimulation is recovered by inhibition of the phosphatidylinositol 3-kinase pathway using LY-294002, suggesting a possible mechanism for the sensitizing effect of caveolin-1. Thus our results suggest that caveolin-1 may act as a coupling or sensitizing factor in signaling apoptotic cell death in both fibroblastic (NIH/3T3) and epithelial (T24) cells.",
keywords = "Caveolae, Caveolin, Signaling",
author = "Jun Liu and Peiyee Lee and Ferruccio Galbiati and Kitsis, {Richard N.} and Lisanti, {Michael P.}",
year = "2001",
language = "English (US)",
volume = "280",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "4 49-4",

}

TY - JOUR

T1 - Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation

AU - Liu, Jun

AU - Lee, Peiyee

AU - Galbiati, Ferruccio

AU - Kitsis, Richard N.

AU - Lisanti, Michael P.

PY - 2001

Y1 - 2001

N2 - The potential role of caveolin-1 in apoptosis remains controversial. Here, we investigate whether caveolin-1 expression is proapoptotic or antiapoptotic using a well-defined antisense approach. We show that NIH/3T3 cells harboring antisense caveolin-1 are resistant to staurosporine-induced apoptosis, as assessed using cell morphology, DNA content, caspase 3 activation, and focal adhesion kinase cleavage. Importantly, sensitivity to apoptosis is recovered when caveolin-1 levels are restored. Conversely, recombinant stable expression of caveolin-1 in T24 bladder carcinoma cells sensitizes these cells to caspase 3 activation. Consistent with the observations using NIH/3T3 cells, downregulation of caveolin-1 in T24 cells substantially diminishes caspase 3-like activity. Loss of sensitivity to apoptotic stimulation is recovered by inhibition of the phosphatidylinositol 3-kinase pathway using LY-294002, suggesting a possible mechanism for the sensitizing effect of caveolin-1. Thus our results suggest that caveolin-1 may act as a coupling or sensitizing factor in signaling apoptotic cell death in both fibroblastic (NIH/3T3) and epithelial (T24) cells.

AB - The potential role of caveolin-1 in apoptosis remains controversial. Here, we investigate whether caveolin-1 expression is proapoptotic or antiapoptotic using a well-defined antisense approach. We show that NIH/3T3 cells harboring antisense caveolin-1 are resistant to staurosporine-induced apoptosis, as assessed using cell morphology, DNA content, caspase 3 activation, and focal adhesion kinase cleavage. Importantly, sensitivity to apoptosis is recovered when caveolin-1 levels are restored. Conversely, recombinant stable expression of caveolin-1 in T24 bladder carcinoma cells sensitizes these cells to caspase 3 activation. Consistent with the observations using NIH/3T3 cells, downregulation of caveolin-1 in T24 cells substantially diminishes caspase 3-like activity. Loss of sensitivity to apoptotic stimulation is recovered by inhibition of the phosphatidylinositol 3-kinase pathway using LY-294002, suggesting a possible mechanism for the sensitizing effect of caveolin-1. Thus our results suggest that caveolin-1 may act as a coupling or sensitizing factor in signaling apoptotic cell death in both fibroblastic (NIH/3T3) and epithelial (T24) cells.

KW - Caveolae

KW - Caveolin

KW - Signaling

UR - http://www.scopus.com/inward/record.url?scp=0034997010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034997010&partnerID=8YFLogxK

M3 - Article

VL - 280

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 4 49-4

ER -