Strathprints logo
Strathprints Home | Open Access | Browse | Search | User area | Copyright | Help | Library Home | SUPrimo

Over-expression of MAP kinase phosphatase-2 enhances adhesion molecule expression and protects against apoptosis in human endothelial cells

Al-Mutairi, Mashael and Al-Harthi, Sameer and Cadalbert, Laurence and Plevin, R.J. (2010) Over-expression of MAP kinase phosphatase-2 enhances adhesion molecule expression and protects against apoptosis in human endothelial cells. British Journal of Pharmacology, 161 (4). pp. 782-798. ISSN 0007-1188

[img]
Preview
PDF (strathprints020126.pdf)
strathprints020126.pdf

Download (1MB) | Preview

Abstract

In this study we used adenovirus infection to overexpress the dual specific phosphatase, MAP kinase phosphatase-2 (MKP-2), in human umbilical vein endothelial cells and examined inflammatory protein expression and apoptosis, two key features of endothelial dysfunction in disease. We generated an adenoviral version of MKP-2 (Adv.MKP-2) and infected HUVECs for 40 h. TNF! stimulated MAP kinase phosphorylation and protein expression was measured by Western blotting. Cellular apoptosis was assayed by FACS. Infection with Adv.MKP-2 selectively abolished TNF!-mediated JNK activation and had little effect upon ERK or p38 MAP kinase. Adv.MKP-2 abrogated COX-2 expression whilst induction of the endothelial cell adhesion molecules ICAM and VCAM, two NF"B-dependent proteins, were not affected. However, when ICAM and VCAM expression was partly reduced by blockage of the NF"B pathway Adv.MKP-2 was able to reverse this inhibition. This correlated with enhanced TNF!-induced I"B! loss, a marker of NF"B activation. TNF! in combination with NF"B blockade also increased HUVEC apoptosis; this was significantly reversed by Adv.MKP-2. Protein markers of cellular damage and apoptosis, H2AX phosphorylation and caspase-3 cleavage, were also reversed by MKP-2 overexpression.

Item type: Article
ID code: 20126
Keywords: map kinase phosphatase-2, endothelial cell dysfunction, caspase, jnk, apoptosis, Therapeutics. Pharmacology, Pharmacy and materia medica, Microbiology, Pharmacology
Subjects: Medicine > Therapeutics. Pharmacology
Medicine > Pharmacy and materia medica
Science > Microbiology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Depositing user: Ms Ann Barker-Myles
Date Deposited: 25 May 2010 13:59
Last modified: 21 Aug 2015 12:03
Related URLs:
URI: http://strathprints.strath.ac.uk/id/eprint/20126

Actions (login required)

View Item View Item