Protein kinase C-β and oxygen deprivation. A novel Egr-1-dependent pathway for fibrin deposition in hypoxemic vasculature

Shi Fang Yan, Jiesheng Lu, Yu Shan Zou, Walter Kisiel, Nigel Mackman, Michael Leitges, Susan Steinberg, David Pinsky, David Stern

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Fibrin deposition is a salient feature of hypoxemic vasculature and results from induction of tissue factor. Such tissue factor expression in an oxygen deficient environment is driven by the transcription factor Early Growth Response (Egr)-1. Using homozygous null mice for the protein kinase C β-isoform gene (PKCβ null), PKCβ is shown to be upstream of Egr-1 in this oxygen deprivation-mediated pathway for triggering procoagulant events. Whereas wild-type mice exposed to hypoxia (6%) displayed a robust increase in tissue factor transcripts and antigen, and vascular fibrin deposition, PKCβ null animals showed a markedly blunted response. Consistent with a central role for Egr-1 in hypoxia-induced expression of tissue factor, PKCβ null mice subjected to oxygen deprivation displayed at most a minor elevation in Egr-1 transcripts, antigen, and intensity of the gel shift band by electrophoretic mobility shift assay, compared with normoxic animals. These data firmly establish PKCβ as a trigger for events leading to induction of Egr-1 and tissue factor under hypoxic conditions, and provide insight into a biologic cascade whereby oxygen deprivation recruits targets of PKCβ and Egr-1, thereby amplifying the cellular response.

Original languageEnglish (US)
Pages (from-to)11921-11928
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number16
DOIs
StatePublished - Apr 21 2000
Externally publishedYes

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Thromboplastin
Fibrin
Protein Kinase C
Oxygen
Growth
Animals
Early Growth Response Protein 1
Antigens
Electrophoretic mobility
Electrophoretic Mobility Shift Assay
Blood Vessels
Assays
Protein Isoforms
Genes
Gels
Hypoxia

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Protein kinase C-β and oxygen deprivation. A novel Egr-1-dependent pathway for fibrin deposition in hypoxemic vasculature. / Yan, Shi Fang; Lu, Jiesheng; Zou, Yu Shan; Kisiel, Walter; Mackman, Nigel; Leitges, Michael; Steinberg, Susan; Pinsky, David; Stern, David.

In: Journal of Biological Chemistry, Vol. 275, No. 16, 21.04.2000, p. 11921-11928.

Research output: Contribution to journalArticle

Yan, Shi Fang ; Lu, Jiesheng ; Zou, Yu Shan ; Kisiel, Walter ; Mackman, Nigel ; Leitges, Michael ; Steinberg, Susan ; Pinsky, David ; Stern, David. / Protein kinase C-β and oxygen deprivation. A novel Egr-1-dependent pathway for fibrin deposition in hypoxemic vasculature. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 16. pp. 11921-11928.
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AU - Pinsky, David

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