Study of the cytotoxicity and antioxidant capacity of N/OFQ(1-13)NH2 and its structural analogues.
The effect of side-chain shortening of N/OFQ(1-13)NH(2) at position 9 ([Orn(9)]N/OFQ(1-13)NH(2), [Dab(9)]N/OFQ(1-13)NH(2), [Dap(9)]N/OFQ(1-13)NH(2)) was studied regarding potential toxicity and antioxidant capacity. Staurosporine- and H2O2-induced damage of SH-SY5Y neuroblastoma cells was not changed in the presence of N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2), but was strongly enhanced in the presence of [Dab(9)]N/OFQ(1-13)NH(2) and [Dap(9)]N/OFQ(1-13)NH(2). Moreover, treatment of cells with the latter two analogues alone led to cell injury. Neuropeptide-dependent differences in the viability of SH-SY5Y cells were also observed, i.e., a cytoprotective effect was observed only in the presence of N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2). Compared to [Dab(9)]N/OFQ(1-13)NH(2) and [Dap(9)]N/OFQ(1-13)NH(2), the effects of N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2) were more beneficial in systems generating free oxygen radicals (O(2)(-) and .OH), as well as on the antioxidant status of rat brain and liver. Taken together, our findings show that N/OFQ(1-13)NH(2) and its structural analogue [Orn(9)]N/OFQ(1-13)NH(2) possess more favorable profiles than the other two nociceptin (N/OFQ) analogues. The present results suggest that shortening of the side-chain of N/OFQ(1-13)NH(2) might increase cell damage and reduce the viability of SH-SY5Y neuroblastoma cells. Moreover, such alterations may lead to changes in free-oxygen generating systems and in antioxidant status in animal tissues.
Kirkova
Margarita
M
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev 23, 1113 Sofia, Bulgaria. simeon@bio.bas.bg
Zamfirova
Rositsa
R
Leśkiewicz
Monika
M
Kubera
Marta
M
Lasoń
Władysław
W
Todorov
Simeon
S
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008297:Male; D009447:Neuroblastoma / Q000378:metabolism; D018847:Opioid Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016877:Oxidants / Q000633:toxicity; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine / Q000633:toxicity
D000975:Antioxidants; D005609:Free Radicals; D018847:Opioid Peptides; D016877:Oxidants; D010446:Peptide Fragments; C439964:nociceptin (1-13) amide; D006861:Hydrogen Peroxide; D019311:Staurosporine