title: Structural characteristics of a lipid peroxidation product, trans-2-nonenal, that favour inhibition of membrane-associated phosphotyrosine phosphatase activity.
abstract: Protein-tyrosine phosphatases (PTPs) are very susceptible to oxidation by reactive oxygen species (ROS), which induce the oxidation of catalytic cysteines, thereby inactivating these PTPs. PTPs are also inactivated by treatment with different aldehydes (such as trans-2-nonenal), produced after tissue damage by ROS. However, the molecular mechanisms behind such aldehyde-due inactivation remain unknown. Using commercially available compounds, we examined the structural characteristics of trans-2-nonenal that allow the inhibition of platelet membrane-associated PTP activity, as well as how these compounds affect the dynamics of SH-, CO- and NH2- protein groups on the membranes. PTP was effectively inhibited by physiological amounts of trans-2-nonenal (1-10 microM). Incubation with trans-2-nonene (10 microM) also decreased PTP activity, although to a lower extent. Treatment with nonyl aldehyde almost eliminated PTP inhibition. Decreases in protein thiols were visible after trans-2-nonenal and trans-2-nonene treatments. Both the latter compounds also increased protein carbonyls (although trans-2-nonenal was more effective) and decreased protein amino groups to an equal extent. Collectively, our data indicate that alpha,beta unsaturation (and not a double bond in another position) is the most important structural determinant for PTP inhibition, the alkenal with 9-carbon atoms being the most effective in eliciting such inhibition. The data allow us to predict the modification of sulfhydryls and/or the formation of addition products with lysyl or histidyl residues, and hence the kind of specific antibodies that it would be necessary to generate in order to test such modifications directly.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Salamanca, Plaza Doctores de la Reina s/n, 37007 Salamanca, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Hernández-Hernández
authors.forename: María N
authors.initials: MN
authors.lastname: Garabatos
authors.forename: Marina C
authors.initials: MC
authors.lastname: Rodríguez
authors.forename: María L
authors.initials: ML
authors.lastname: Vidal
authors.forename: Abel
authors.initials: A
authors.lastname: López-Revuelta
authors.forename: José I
authors.initials: JI
authors.lastname: Sánchez-Gallego
authors.forename: Marcial
authors.initials: M
authors.lastname: Llanillo
authors.forename: Jesús
authors.initials: J
authors.lastname: Sánchez-Yagüe
mesh_terms: D000447:Aldehydes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000588:Amines / Q000032:analysis; D001792:Blood Platelets / Q000187:drug effects; D002244:Carbon / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D015227:Lipid Peroxidation; D008565:Membrane Proteins / Q000737:chemistry; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000032:analysis
chemical_list: D000447:Aldehydes; D000588:Amines; D008565:Membrane Proteins; D013438:Sulfhydryl Compounds; C013166:2-nonenal; D002244:Carbon; D017027:Protein Tyrosine Phosphatases