Hernandez Mar, Solé Montse, Boada Mercè, Unzeta Mercedes
Departament de Bioquímica i Biologia Molecular, Institut de Neurociències, Facultat de Medicina, Universitat Autònoma de Barcelona, (08193) Bellaterra, Barcelona, Spain.
Biochim Biophys Acta. 2006 Feb;1763(2):164-73. doi: 10.1016/j.bbamcr.2005.11.017. Epub 2006 Jan 6.
Semicarbazide sensitive amine oxidase (SSAO) metabolizes oxidative deamination of primary aromatic and aliphatic amines. It is selectively expressed in vascular cells of blood vessels, but it is also circulating in blood plasma. SSAO activity in plasma is increased in some diseases associated with vascular complications and its catalytic products may cause tissue damage. We examined the effect of the oxidation of the SSAO substrate, methylamine, on cultured smooth muscle cells. Cell incubation with methylamine plus soluble SSAO, contained in bovine serum, resulted toxic to rat aorta A7r5 and human aortic smooth muscle cells, as measured by MTT reduction. This effect was completely reverted by specific SSAO inhibitors, indicating that the toxicity was mediated by the end products generated. Moreover, SSAO-mediated deamination of methylamine induced apoptosis in A7r5 cells, detected by chromatin condensation, Caspase-3 activation, PARP cleavage and cytochrome c release to cytosol. Formaldehyde, rather than H2O2, resulted to be a strong apoptotic inducer to A7r5 cells. Taken together, the results suggest that increased plasma SSAO activity in pathological conditions, could contribute to apoptosis in smooth muscle cells, leading to vascular tissue damage.
氨基脲敏感胺氧化酶（SSAO）可代谢伯芳香胺和脂肪胺的氧化脱氨反应。它在血管的血管细胞中选择性表达，但也存在于血浆中循环。血浆中的SSAO活性在一些与血管并发症相关的疾病中会升高，其催化产物可能会导致组织损伤。我们研究了SSAO底物甲胺的氧化对培养的平滑肌细胞的影响。用甲胺加牛血清中所含的可溶性SSAO孵育细胞，通过MTT还原法测定，结果显示对大鼠主动脉A7r5细胞和人主动脉平滑肌细胞有毒性。这种作用可被特异性SSAO抑制剂完全逆转，表明毒性是由生成的终产物介导的。此外，SSAO介导的甲胺脱氨作用可诱导A7r5细胞凋亡，通过染色质浓缩、半胱天冬酶-3激活、聚（ADP-核糖）聚合酶（PARP）裂解以及细胞色素c释放到细胞质中检测到。甲醛而非过氧化氢是A7r5细胞强烈的凋亡诱导剂。综上所述，结果表明在病理条件下血浆SSAO活性增加可能导致平滑肌细胞凋亡，进而导致血管组织损伤。
