Yu P H, Zuo D M
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Atherosclerosis. 1996 Feb;120(1-2):189-97. doi: 10.1016/0021-9150(95)05701-3.
Methylamine can be converted by semicarbazide-sensitive amine oxidase (SSAO) to formaldehyde and hydrogen peroxide, which have been proven to be toxic towards cultured endothelial cells. We investigated whether or not these deaminated products from methylamine can exert potentially hazardous toxic effects in vivo. Long lasting residual radioactivity in different tissues was detected following administration of [14C]-methylamine in the mouse. Approximately 10% of the total administered radioactivity could even be detected 5 days after injection of [14C]-methylamine. Eighty percent of the formation of irreversible adducts can be blocked by a highly selective SSAO inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A). The residual radioactivity was primarily associated with the insoluble tissue components and the soluble macromolecules. Radioactively labelled macromolecules were fragmented following enzymatic proteolysis. Results suggest that the formaldehyde derived from methylamine interacts with proteins in vivo. In the streptozotocin-induced diabetic mice, both SSAO activity and the formation of residual radioactivity were found to be significantly increased in the kidney. Chronic administration of methylamine enhances blood prorenin level, which strongly suggests that uncontrolled deamination of methylamine may be a risk factor for initiation of endothelial injury, and subsequent genesis of atherosclerosis.
甲胺可被氨基脲敏感胺氧化酶（SSAO）转化为甲醛和过氧化氢，事实证明这两种物质对培养的内皮细胞有毒性。我们研究了甲胺的这些脱氨产物在体内是否会产生潜在的有害毒性作用。给小鼠注射[14C] -甲胺后，在不同组织中检测到了持久的残留放射性。在注射[14C] -甲胺5天后，甚至可以检测到约10%的总给药放射性。80%的不可逆加合物形成可被一种高度选择性的SSAO抑制剂（E）-2-（4-氟苯乙基）-3-氟烯丙胺盐酸盐（MDL-72974A）阻断。残留放射性主要与不溶性组织成分和可溶性大分子相关。放射性标记的大分子在酶促蛋白水解后会断裂。结果表明，甲胺衍生的甲醛在体内与蛋白质相互作用。在链脲佐菌素诱导的糖尿病小鼠中，发现肾脏中的SSAO活性和残留放射性形成均显著增加。长期给予甲胺会提高血液中前肾素水平，这强烈表明甲胺不受控制的脱氨可能是引发内皮损伤及随后动脉粥样硬化发生的一个危险因素。
