Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells

Citation
Mw. Lame et al., Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells, J BIOL CHEM, 275(37), 2000, pp. 29091-29099
Citations number
90
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
37
Year of publication
2000
Pages
29091 - 29099
Database
ISI
SICI code
0021-9258(20000915)275:37<29091:PTOMPI>2.0.ZU;2-N
Abstract
A single administration of monocrotaline to rats results in pathologic alte rations in the lung and heart similar to human pulmonary hypertension. In o rder to produce these lesions, monocrotaline is oxidized to monocrotaline p yrrole in the liver followed by hematogenous transport to the lung where it injures pulmonary endothelium. In this study, we determined specific endot helial targets for C-14-monocrotaline pyrrole using two-dimensional gel ele ctrophoresis 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 matr ix-assisted laser desorption ionization mass spectrometry, The results were searched against sequence data bases to identify the adducted proteins, Fi ve abundant adducted proteins were identified as galectin-1, protein-disulf ide isomerase, probable protein-disulfide isomerase (ER60), beta- or gamma- cytoplasmic actin, and cytoskeletal tropomyosin (TM30-NM). With the excepti on of actin, the proteins identified in this study have never been identifi ed as potential targets for pyrroles, and the majority of these proteins ha ve either received no or minimal attention as targets for other electrophil ic compounds. The known functions of these proteins are discussed in terms of their potential for explaining the pulmonary toxicity of monocrotaline.