2-Deoxy-D-ribose-induced oxidative stress causes apoptosis in human monocytic cells: prevention by pyridoxal-5'-phosphate.
Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis of diabetic complications. Although some clinical evidences suggest the use of pyridoxal-5'-phosphate (PLP) in diabetes with nephropathy, the exact mechanism of PLP has not been fully understood. In the present study, the effect of PLP on 2-deoxy-D-ribose (dRib)-induced oxidative damages and apoptosis on human monocytic cells (U937) was investigated. U937 cells exposed to dRib (30 mM) exhibited abnormal properties, including loss pf cell viability, overproduction of reactive oxygen species (ROS), glutathione depletion and some biochemical features of apoptosis. Treatment with PLP at two effective concentrations (100 and 250 microM) strongly inhibited ROS production and glutathione depletion in dRib-treated U937 cells. The extent of Lipid peroxidation and protein oxidation was also decreased in the presence of PLP. In addition, PLP suppressed dRib-induced apoptotic criteria such as sub-G1 apoptotic population and annexin-V staining. The use of N-acetylcysteine (NAC), a thiol antioxidant and GSH precursor, prevented the extent of apoptosis. The results demonstrate that dRib induces the generation of ROS leading to dRib-mediated apoptosis which can be attenuated by PLP through antioxidant mechanisms.
Ardestani
Amin
A
Institute of Biochemistry and Biophysics, PO Box 13145-1384, University of Tehran, Tehran, Iran.
Yazdanparast
Razieh
R
Nejad
Abdolfattah Sarraf
AS
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003855:Deoxyribose / Q000633:toxicity*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009000:Monocytes / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014803:Vitamin B Complex / Q000494:pharmacology*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014803:Vitamin B Complex; D003855:Deoxyribose; D011732:Pyridoxal Phosphate; D005978:Glutathione