Tumor Necrosis Factor-Mediated Effects on Gamma-Glutamyl Transpeptidase Activity in Cloned Cerebral Endothelial Cells

V. McGovern, H. C. Bauer, C. J. McClain, B. Jackson, B. Henmig

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Gamma-glutamyl transpeptidase (γ-GTP), a marker enzyme for blood brain barrier (BBB) function, was induced consistently by TNF (500 U/mL) in cerebral endothelial cells (cEC) compared with control cultures. The enzyme activity was found to be considerably lower in pulmonary artery cells, where, when treated with TNF (500 U/mL), the induction was not observed. Pre-incubation with zinc (1 μg/mL)-enriched media for 48 hours did not block TNF-mediated activation of γ-GTP. The increase in γ-GTP activity does not appear to be mediated through the cAMP signal transduction pathway as evidenced by the lack of TNF-mediated intracellular accumulation of cAMP. In addition, forskolin failed to influence γ-GTP enzyme activity, which further suggests that cAMP is not involved. Phospholipase A2, an enzyme involved in the arachidonic acid pathway, appears to be implicated in TNF signalling across the membrane of cEC. Two inhibitors of phospholipase A2, mepacrine and p-bromophenacyl-bromide (BPB), depressed the activity of γ-GTP in the presence of TNF. These data suggest that an important relationship exists between γ-GTP activity and TNF-induced dysfunction of the cerebral endothelium. This may have implications in understanding cytokine-mediated alterations in BBB function.

Original languageEnglish
Pages (from-to)143-148
Number of pages6
JournalEndothelium: Journal of Endothelial Cell Research
Issue number2
StatePublished - Jan 1 1994

Bibliographical note

Funding Information:
Supported in part by grants 1PO1 HL36.552 from the National Institutes of Health, Veterans' Admjnistra-tion and the General Clinical Research Center M01 RR 02602-08, Universii.y of Kentucky, grants from the National Dairy Promotion and Research Board, National Dairy Council, American Heart Association, Kentucky Affiliate, University of Kentucky Medical Center Research Grant 93-648, grants 8304 and 8289 from the Austrian FWF, and the Kentucky Agricultural Experiment Station (article number 93-9-144).


  • Cerebral endothelial cells
  • Cyclic AMP
  • Gamma-glutamyl transpeptidase
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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