Inhibition of radiation induced nitration by curcumin and nicotinamide in mouse macrophages

Nitric oxide plays an important role in inflammation and carcinogenesis and has now been implicated as an important signaling molecule under normal physiological conditions also. Increased nitric oxide (NO) results in increased nitration of proteins at tyrosine, which can cause protein dysfunction or alterations in signal transduction pathways. Irradiation of Lipopolysaccharide (LPS) activated mouse peritoneal macrophages was found to increase NO production, inducible nitric oxide synthase (iNOS) expression and nitration of proteins. The increase in iNOS expression was very less when compared to increase in NO production, indicating the possibility of post-translational activation of iNOS by LPS and ionising radiation. The addition of curcumin, nicotinamide and Jun N-terminal kinase (JNK) inhibitor, SP 600125, reduced the levels of NO, iNOS expression and nitration of proteins in macrophages. Closer scrutiny of the inhibition pattern of these modulators revealed that although the JNK inhibitor did not result in significant decrease in iNOS expression it led to a significant decrease in NO production, implying the possible involvement of JNK in the regulation of iNOS activity. Curcumin and JNK inhibitor directly inhibited the nitration of proteins and JNK inhibitor and curcumin, when added together, did not show synergistic effect.