Indoxyl sulfate induces apoptosis in mononuclear blood cells via mitochondrial pathway.
Anna PieniazekJoanna Bernasinska-SlomczewskaPawel HikiszPublished in: Scientific reports (2023)
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.
Keyphrases
- induced apoptosis
- oxidative stress
- dna damage
- endoplasmic reticulum stress
- cell death
- cell cycle arrest
- poor prognosis
- dna repair
- chronic kidney disease
- signaling pathway
- escherichia coli
- binding protein
- end stage renal disease
- cell proliferation
- combination therapy
- replacement therapy
- pi k akt
- anti inflammatory
- climate change