The FASEB Journal, Vol 8, 529-533, Copyright © 1994 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Nitric oxide generation from streptozotocin

NS Kwon, SH Lee, CS Choi, T Kho and HS Lee
Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul, Korea.

Streptozotocin (STZ), a diabetogenic agent, is thought to damage pancreatic beta-cells by activating immune mechanisms and by alkylating DNA. In the present study, we demonstrated that STZ can produce nitric oxide (NO), a bioregulatory and cytotoxic molecule. When STZ was dissolved in a sodium phosphate buffer (50 mM, pH 7.4) and irradiated with a 22 W circular fluorescent light, nitrite and nitrate, stable oxidation products of NO, were produced. The wavelengths of light most responsible for the photo-decomposition were 300-310 nm and 410-420 nm. When a mixture of reduced hemoglobin and STZ was irradiated with UV light (280-320 nm), hemoglobin underwent characteristic NO-dependent spectral changes. STZ relaxed deendothelialized aortic strips only in the presence of light. STZ/light-dependent relaxation was attenuated by reduced hemoglobin. These results indicated photo-induced NO production from STZ. NO generation depended on the concentration of STZ, the duration of irradiation, and the distance between sample and light source. In acidic conditions, NO production from STZ was spontaneous even in the dark. Light-independent NO generation was augmented by increasing acidity, and markedly diminished in a D2O-based buffer, indicating the involvement of protons in the mechanism of STZ decomposition in acid. These results imply the usefulness of STZ as an NO-generating reagent, and indicate that direct NO-generation may be a mechanism of STZ toxicity in diabetogenesis.

This article has been cited by other articles:

				A. P. Martin, J. M. Alexander-Brett, C. Canasto-Chibuque, A. Garin, J. S. Bromberg, D. H. Fremont, and S. A. Lira The Chemokine Binding Protein M3 Prevents Diabetes Induced by Multiple Low Doses of Streptozotocin J. Immunol., April 1, 2007; 178(7): 4623 - 4631. [Abstract] [Full Text] [PDF]

				R. Hagerkvist, S. Sandler, D. Mokhtari, and N. Welsh Amelioration of diabetes by imatinib mesylate (Gleevec(R)): role of {beta}-cell NF-{kappa}B activation and anti-apoptotic preconditioning FASEB J, February 1, 2007; 21(2): 618 - 628. [Abstract] [Full Text] [PDF]

				A K Katakam, G Chipitsyna, Q Gong, A R Vancha, J Gabbeta, and H A Arafat Streptozotocin (STZ) mediates acute upregulation of serum and pancreatic osteopontin (OPN): a novel islet-protective effect of OPN through inhibition of STZ-induced nitric oxide production J. Endocrinol., November 1, 2005; 187(2): 237 - 247. [Abstract] [Full Text] [PDF]

				S.-J. Zheng, S.-E. Lamhamedi-Cherradi, P. Wang, L. Xu, and Y. H. Chen Tumor Suppressor p53 Inhibits Autoimmune Inflammation and Macrophage Function Diabetes, May 1, 2005; 54(5): 1423 - 1428. [Abstract] [Full Text] [PDF]

				C. S. Park, H. Lim, K. J. Han, S. H. Baek, H. O. Sohn, D. W. Lee, Y.-G. Kim, H.-Y. Yun, K. J. Baek, and N. S. Kwon Inhibition of Nitric Oxide Generation by 23,24-Dihydrocucurbitacin D in Mouse Peritoneal Macrophages J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 705 - 710. [Abstract] [Full Text] [PDF]

				S.-E. Lamhamedi-Cherradi, S. Zheng, B. A. Hilliard, L. Xu, J. Sun, S. Alsheadat, H.-C. Liou, and Y. H. Chen Transcriptional Regulation of Type I Diabetes by NF-{kappa}B J. Immunol., November 1, 2003; 171(9): 4886 - 4892. [Abstract] [Full Text] [PDF]

				G. M. Pieper Review of Alterations in Endothelial Nitric Oxide Production in Diabetes : Protective Role of Arginine on Endothelial Dysfunction Hypertension, May 1, 1998; 31(5): 1047 - 1060. [Full Text] [PDF]