American University of Health Sciences, Signal Hill, CA, 90755, USA.
University of California, Irvine, CA, USA.
Inflammopharmacology. 2024 Dec;32(6):3739-3744. doi: 10.1007/s10787-024-01551-7. Epub 2024 Sep 12.
Cysteamine (CA) induces duodenal ulcers in rodents (Selye and Szabo, Nature 244:458-459, 1973). Cysteine (Cys), a precursor for the formation of CA (via catabolism of coenzyme A), does not cause lesions in the duodenum (Szabo et al., J Pharmacol Exp Ther 223:68-76, 1982). CA also has antimutagenic and anticancer pharmacology (Fujisawa et al., PLoS ONE 7, 2012; Lee, Adv Pharmacol Pharm Sci 2023:2419444, 2023). We propose a mechanism of CA-induced cell death dependent on oxygen and CA dioxygenase (ADO) that can explain the 50-year-old mystery as to why CA is, but Cys is not, ulcerogenic. Those cells expressing coenzyme A-catabolizing enzymes are subject to a unique type of oxygen- and enzyme-bound-Fe-dependent death, type II ferroptosis.
半胱胺（CA）可诱导啮齿动物发生十二指肠溃疡（Selye 和 Szabo，《自然》244:458-459, 1973）。半胱氨酸（Cys）是 CA 形成的前体（通过辅酶 A 的分解代谢），不会在十二指肠中引起病变（Szabo 等人，《美国药理学与实验治疗学杂志》223:68-76, 1982）。CA 还具有抗突变和抗癌药理学特性（Fujisawa 等人，《公共科学图书馆·综合》7, 2012；Lee，《药理学与药物科学进展》2023:2419444, 2023）。我们提出了一种依赖于氧和 CA 加双氧酶（ADO）的 CA 诱导细胞死亡的机制，该机制可以解释存在 50 年之久的谜团，即为什么 CA 是致溃疡的，但 Cys 不是。那些表达辅酶 A 分解代谢酶的细胞容易受到一种独特的、与氧和酶结合的铁依赖性死亡的影响，即 II 型铁死亡。
