Pharmacologically activated migration of aortic endothelial cells is mediated through p38 SAPK

László Dénes, Andrea Jednákovits, Judit Hargitai, Zoltán Pénzes, A. Balla, László Tálosi, Péter Krajcsi, P. Csermely

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

1. Impairment in endothelial cell (EC) function plays a central role in vascular diseases (e.g. atherosclerosis, restenosis, diabetic angiopathies, microvascular angina, peripheral arterial disease). BRX-235 (a novel small molecule synthesized by Biorex, Hungary) has a potent vasculoprotective activity in different in vivo and in vitro studies. Since the importance of the p38 pathway in EC homeostasis and migration in particular is well documented, we have carried out studies to address the role of the p38 stress activated protein kinase (p38 SAPK) in the mode of action of BRX-235. In this study, Bovine aortic endothelial cells were used in a wounding migration assay (WMA) and for Western-blot analysis to study the effect and molecular mechanism of BRX-235-induced EC migration. 2. The bovine aortic endothelial (BAE) cells were shown to be good models for EC migration. 3. Both endothelial cell growth factor (ECGF)- and BRX-235-induced BAE cell migration were shown to be inhibited by SB 203580, a specific inhibitor of p38 SAPK. 4. It was also shown that, BRX-235 induces phosphorylation of p38 SAPK without affecting p38 SAPK protein levels. Thus, BRX-235 acts upstream of p38 SAPK. 5. In summary, we have shown that p38 SAPK is a potential pharmacological mediator for candidate drugs that target the endothelium.

Original languageEnglish
Pages (from-to)597-603
Number of pages7
JournalBritish Journal of Pharmacology
Volume136
Issue number4
Publication statusPublished - 2002

Fingerprint

Heat-Shock Proteins
Protein Kinases
Endothelial Cells
Cell Movement
Microvascular Angina
Endothelial Growth Factors
Diabetic Angiopathies
Hungary
Peripheral Arterial Disease
Vascular Diseases
Endothelium
iroxanadine
Atherosclerosis
Homeostasis
Western Blotting
Phosphorylation
Pharmacology
Pharmaceutical Preparations

Keywords

  • Bovine aortic endothelial cell
  • BRX-235 (Biorex, Hungary)
  • Migration
  • p38 SAPK
  • Phosphorylated-p38 SAPK
  • Wounding migration assay

ASJC Scopus subject areas

  • Pharmacology

Cite this

Pharmacologically activated migration of aortic endothelial cells is mediated through p38 SAPK. / Dénes, László; Jednákovits, Andrea; Hargitai, Judit; Pénzes, Zoltán; Balla, A.; Tálosi, László; Krajcsi, Péter; Csermely, P.

In: British Journal of Pharmacology, Vol. 136, No. 4, 2002, p. 597-603.

Research output: Contribution to journalArticle

Dénes, L, Jednákovits, A, Hargitai, J, Pénzes, Z, Balla, A, Tálosi, L, Krajcsi, P & Csermely, P 2002, 'Pharmacologically activated migration of aortic endothelial cells is mediated through p38 SAPK', British Journal of Pharmacology, vol. 136, no. 4, pp. 597-603.
Dénes L, Jednákovits A, Hargitai J, Pénzes Z, Balla A, Tálosi L et al. Pharmacologically activated migration of aortic endothelial cells is mediated through p38 SAPK. British Journal of Pharmacology. 2002;136(4):597-603.
Dénes, László ; Jednákovits, Andrea ; Hargitai, Judit ; Pénzes, Zoltán ; Balla, A. ; Tálosi, László ; Krajcsi, Péter ; Csermely, P. / Pharmacologically activated migration of aortic endothelial cells is mediated through p38 SAPK. In: British Journal of Pharmacology. 2002 ; Vol. 136, No. 4. pp. 597-603.
@article{2fce96ef49524fdeba1bff2365a80df3,
title = "Pharmacologically activated migration of aortic endothelial cells is mediated through p38 SAPK",
abstract = "1. Impairment in endothelial cell (EC) function plays a central role in vascular diseases (e.g. atherosclerosis, restenosis, diabetic angiopathies, microvascular angina, peripheral arterial disease). BRX-235 (a novel small molecule synthesized by Biorex, Hungary) has a potent vasculoprotective activity in different in vivo and in vitro studies. Since the importance of the p38 pathway in EC homeostasis and migration in particular is well documented, we have carried out studies to address the role of the p38 stress activated protein kinase (p38 SAPK) in the mode of action of BRX-235. In this study, Bovine aortic endothelial cells were used in a wounding migration assay (WMA) and for Western-blot analysis to study the effect and molecular mechanism of BRX-235-induced EC migration. 2. The bovine aortic endothelial (BAE) cells were shown to be good models for EC migration. 3. Both endothelial cell growth factor (ECGF)- and BRX-235-induced BAE cell migration were shown to be inhibited by SB 203580, a specific inhibitor of p38 SAPK. 4. It was also shown that, BRX-235 induces phosphorylation of p38 SAPK without affecting p38 SAPK protein levels. Thus, BRX-235 acts upstream of p38 SAPK. 5. In summary, we have shown that p38 SAPK is a potential pharmacological mediator for candidate drugs that target the endothelium.",
keywords = "Bovine aortic endothelial cell, BRX-235 (Biorex, Hungary), Migration, p38 SAPK, Phosphorylated-p38 SAPK, Wounding migration assay",
author = "L{\'a}szl{\'o} D{\'e}nes and Andrea Jedn{\'a}kovits and Judit Hargitai and Zolt{\'a}n P{\'e}nzes and A. Balla and L{\'a}szl{\'o} T{\'a}losi and P{\'e}ter Krajcsi and P. Csermely",
year = "2002",
language = "English",
volume = "136",
pages = "597--603",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Pharmacologically activated migration of aortic endothelial cells is mediated through p38 SAPK

AU - Dénes, László

AU - Jednákovits, Andrea

AU - Hargitai, Judit

AU - Pénzes, Zoltán

AU - Balla, A.

AU - Tálosi, László

AU - Krajcsi, Péter

AU - Csermely, P.

PY - 2002

Y1 - 2002

N2 - 1. Impairment in endothelial cell (EC) function plays a central role in vascular diseases (e.g. atherosclerosis, restenosis, diabetic angiopathies, microvascular angina, peripheral arterial disease). BRX-235 (a novel small molecule synthesized by Biorex, Hungary) has a potent vasculoprotective activity in different in vivo and in vitro studies. Since the importance of the p38 pathway in EC homeostasis and migration in particular is well documented, we have carried out studies to address the role of the p38 stress activated protein kinase (p38 SAPK) in the mode of action of BRX-235. In this study, Bovine aortic endothelial cells were used in a wounding migration assay (WMA) and for Western-blot analysis to study the effect and molecular mechanism of BRX-235-induced EC migration. 2. The bovine aortic endothelial (BAE) cells were shown to be good models for EC migration. 3. Both endothelial cell growth factor (ECGF)- and BRX-235-induced BAE cell migration were shown to be inhibited by SB 203580, a specific inhibitor of p38 SAPK. 4. It was also shown that, BRX-235 induces phosphorylation of p38 SAPK without affecting p38 SAPK protein levels. Thus, BRX-235 acts upstream of p38 SAPK. 5. In summary, we have shown that p38 SAPK is a potential pharmacological mediator for candidate drugs that target the endothelium.

AB - 1. Impairment in endothelial cell (EC) function plays a central role in vascular diseases (e.g. atherosclerosis, restenosis, diabetic angiopathies, microvascular angina, peripheral arterial disease). BRX-235 (a novel small molecule synthesized by Biorex, Hungary) has a potent vasculoprotective activity in different in vivo and in vitro studies. Since the importance of the p38 pathway in EC homeostasis and migration in particular is well documented, we have carried out studies to address the role of the p38 stress activated protein kinase (p38 SAPK) in the mode of action of BRX-235. In this study, Bovine aortic endothelial cells were used in a wounding migration assay (WMA) and for Western-blot analysis to study the effect and molecular mechanism of BRX-235-induced EC migration. 2. The bovine aortic endothelial (BAE) cells were shown to be good models for EC migration. 3. Both endothelial cell growth factor (ECGF)- and BRX-235-induced BAE cell migration were shown to be inhibited by SB 203580, a specific inhibitor of p38 SAPK. 4. It was also shown that, BRX-235 induces phosphorylation of p38 SAPK without affecting p38 SAPK protein levels. Thus, BRX-235 acts upstream of p38 SAPK. 5. In summary, we have shown that p38 SAPK is a potential pharmacological mediator for candidate drugs that target the endothelium.

KW - Bovine aortic endothelial cell

KW - BRX-235 (Biorex, Hungary)

KW - Migration

KW - p38 SAPK

KW - Phosphorylated-p38 SAPK

KW - Wounding migration assay

UR - http://www.scopus.com/inward/record.url?scp=0035984947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035984947&partnerID=8YFLogxK

M3 - Article

C2 - 12055138

AN - SCOPUS:0035984947

VL - 136

SP - 597

EP - 603

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 4

ER -