Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells

Michael W. Lamé, A. Daniel Jones, Dennis W Wilson, Sheryl K. Dunston, H. J. Segall

Research output: Contribution to journalArticle

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Abstract

A single administration of monocrotaline to rats results in pathologic alterations in the lung and heart similar to human pulmonary hypertension. In order to produce these lesions, monocrotaline is oxidized to monocrotaline pyrrole in the liver followed by hematogenous transport to the lung where it injures pulmonary endothelium. In this study, we determined specific endothelial targets for 14C-monocrotaline pyrrole using two-dimensional gel electrophoresis and autoradiographic detection of protein metabolite adducts. Selective labeling of specific proteins was observed. Labeled proteins were digested with trypsin, and the resulting peptides were analyzed using matrix-assisted laser desorption ionization mass spectrometry. The results were searched against sequence data bases to identify the adducted proteins. Five abundant adducted proteins were identified as galectin-1, protein-disulfide isomerase, probable protein-disulfide isomerase (ER60), β- or γ-cytoplasmic actin, and cytoskeletal tropomyosin (TM30-NM). With the exception of actin, the proteins identified in this study have never been identified as potential targets for pyrroles, and the majority of these proteins have either received no or minimal attention as targets for other electrophilic compounds. The known functions of these proteins are discussed in terms of their potential for explaining the pulmonary toxicity of monocrotaline.

Original languageEnglish (US)
Pages (from-to)29091-29099
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number37
StatePublished - Sep 15 2000

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Endothelial cells
Pulmonary Artery
Endothelial Cells
Monocrotaline
Proteins
Protein Disulfide-Isomerases
Lung
Actins
Galectin 1
Tropomyosin
Pyrroles
monocrotaline pyrrole
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Electrophoresis, Gel, Two-Dimensional
Metabolites
Electrophoresis
Pulmonary Hypertension
Liver
Trypsin
Labeling

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lamé, M. W., Jones, A. D., Wilson, D. W., Dunston, S. K., & Segall, H. J. (2000). Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells. Journal of Biological Chemistry, 275(37), 29091-29099.

Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells. / Lamé, Michael W.; Jones, A. Daniel; Wilson, Dennis W; Dunston, Sheryl K.; Segall, H. J.

In: Journal of Biological Chemistry, Vol. 275, No. 37, 15.09.2000, p. 29091-29099.

Research output: Contribution to journalArticle

Lamé, MW, Jones, AD, Wilson, DW, Dunston, SK & Segall, HJ 2000, 'Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells', Journal of Biological Chemistry, vol. 275, no. 37, pp. 29091-29099.
Lamé, Michael W. ; Jones, A. Daniel ; Wilson, Dennis W ; Dunston, Sheryl K. ; Segall, H. J. / Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 37. pp. 29091-29099.
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