Induction of resistance to TNF cytotoxicity and mitochondrial superoxide dismutase on U-937 cells by 1,25-dihydroxyvitamin D3.
1,25-dihydroxyvitamin D3 (1,25(OH)2D3) dose-dependently inhibited the cytotoxicity of tumor necrosis factor (TNF) in a human monoblastic leukemic cell line, U-937. Combination of TNF and 1,25(OH)2D3 remarkably increased mitochondrial superoxide dismutase (mSOD) of U-937 cells, TNF alone increased it only slightly and 1,25(OH)2D3 alone did not. The cytosolic SOD (cSOD) activity was not changed by TNF or/and 1,25(OH)2D3. The mSOD activity was not inhibited by 2 mM KCN, suggesting that mSOD should be a manganese SOD (MnSOD). These results suggest that 1,25(OH)2D3 may reduce the susceptibility to TNF cytotoxicity of U-937 cells by enhancing the ability of inducing MnSOD by TNF.
Iwamoto
S
S
1st Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
Takeda
K
K
Kamijo
R
R
Konno
K
K
D002117:Calcitriol / Q000494:pharmacology*; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000201:enzymology*; D008928:Mitochondria / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase; D002117:Calcitriol