Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, Ul. Pomorska 141/143, 90-236, Lodz, Poland.
Sci Rep. 2023 Aug 28;13(1):14044. doi: 10.1038/s41598-023-40824-z.
The consequence of chronic kidney disease is the accumulation of metabolic products called uremic toxins in the body. Indoxyl sulfate (IS) is a toxin with a high affinity for proteins. This study focuses on the deleterious effect of IS, especially apoptosis induction, in mononuclear blood cells (MNCs). Thus, in MNCs treated with IS at three different concentrations for 24 h, the survival, mitochondrial potential, caspases activity and expression, Bcl-2 and Bax protein expression, DNA damage, and PARP degradation were estimated. The study showed a decrease in survival and mitochondrial potential of MNCs treated with IS compared to the control. IS increased the activity of caspase 2-, 3-, 9-, and the expression of caspase 3-, and 9- in MNCs but does not affect the activity of caspase 6- and 8. The treatment of MNCs with IS also increased DNA damage and degradation of PARP. Indoxyl sulfate significantly influences the expression of Bcl-2 and Bax proteins. Indoxyl sulfate induces the programmed death of MNCs through the intrinsic mitochondrial apoptotic pathway. The observed cellular changes are mostly dose-dependent.
慢性肾脏病的后果是体内代谢产物（称为尿毒症毒素）的积累。硫酸吲哚酚（IS）是一种与蛋白质亲和力高的毒素。本研究重点关注 IS 的有害作用，特别是诱导单核细胞（MNC）凋亡。因此，在三个不同浓度的 IS 处理单核细胞 24 小时后，评估了细胞存活率、线粒体电位、半胱天冬酶活性和表达、Bcl-2 和 Bax 蛋白表达、DNA 损伤和 PARP 降解。研究表明，与对照组相比，IS 处理的单核细胞存活率和线粒体电位降低。IS 增加了 MNC 中 caspase-2、3、9 的活性和 caspase-3、9 的表达，但不影响 caspase-6 和 8 的活性。IS 处理还增加了 MNC 的 DNA 损伤和 PARP 降解。硫酸吲哚酚显著影响 Bcl-2 和 Bax 蛋白的表达。硫酸吲哚酚通过内在的线粒体凋亡途径诱导 MNC 的程序性死亡。观察到的细胞变化大多是剂量依赖性的。
