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)
Download (1402Kb) | 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
    Related URLs:
    Depositing user: Ms Ann Barker-Myles
    Date Deposited: 25 May 2010 14:59
    Last modified: 27 Mar 2014 21:01
    URI: http://strathprints.strath.ac.uk/id/eprint/20126

    Actions (login required)

    View Item

    Fulltext Downloads: