p53 phosphorylation is involved in vascular cell death induced by the catalytic activity of membrane-bound SSAO/VAP-1

Semicarbazide sensitive amine oxidase (SSAO) is a multifunctional enzyme present mainly in adipocytes, endothelial and smooth muscle cells. It metabolizes primary aliphatic and aromatic amines generating products able to contribute to cellular oxidative stress. SSAO is expressed in a membrane-bound form and is also present as a soluble enzyme in plasma. Both isoforms are increased in several pathologies, and the catalytic products generated by the soluble enzymatic activity can induce cytotoxicity of vascular cells in culture. We have analyzed whether the transmembrane form of the enzyme is able to produce a cytotoxic effect through methylamine oxidation. Since cells in culture lose the expression of this enzyme, we used an SSAO stably transfected smooth muscle cell line. Herein we report that cell treatment with the substrate methylamine induced a dose and time dependent cytotoxic effect. The tumor suppressor protein p53 played an important role in the molecular pathway involved in this cell death. Moreover, we also observed the induction of PUMA-α expression with mitochondrial Bcl-2 family proteins being affected, and final effector caspases being activated.