Effects of 1-methylnicotinamide and its metabolite N-methyl-2-pyridone-5-carboxamide on streptozotocin-induced toxicity in murine insulinoma MIN6 cell line

• Autorzy: Przygodzki T. , Slominska E. , Polakowska E. , Mlynarski W. , Watala C.
• Języki publikacji: EN

Abstrakty

EN

 1-methylnicotinamide (MNA) is a primary metabolite of nicotinamide. In recent years several activities of MNA have been described, such as anti-inflammatory activity in skin diseases, induction of prostacyclin synthesis via COX-2, aortal endothelium protection in diabetes and hypertriglyceridaemia and increased survival rate of diabetic rats. 1-methylnicotinamide was also suggested to protect pancreatic cells from streptozotocin in vivo. Streptozotocin toxicity is known to be mediated by poly-ADP-ribose polymerase. Nicotinamide and its derivatives have been shown to ameliorate poly-ADP-ribose polymerase-dependent nucleotide pool reduction. We aimed to verify if 1-methylnicotinamide and its metabolite, N-methyl-2-pyridone-5-carboxamide, can protect insulinoma cells from streptozotocin-induced toxicity. We found that N-methyl-2-pyridone-5-carboxamide, but not 1-methylnicotinamide, restores the pool of ATP and NAD+ in streptozotocin-treated cells, but neither compound improved the cell viability. We conclude that inhibition of poly-ADP-ribose polymerase-dependent nucleotide pool reduction may not be sufficient to protect cells from streptozotocin toxicity.

Słowa kluczowe

EN

1-methylnicotinamide; MIN6 cell line; N-methyl-2-pyridone-5-carboxamide; diabetes; murine insulinoma; nicotinamide; nucleotide pool; poly[ADP-ribose] polymerase; primary metabolite; skin disease; streptozotocin; toxicity; mice; mouse

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2011
• Tom: 58
• Numer: 1
• Opis fizyczny: p.75-77,fig.,ref.

Twórcy

autor

Przygodzki T.

• Department of Haemostasis and Haemostatic Disorders, Chair of Laboratory Diagnostics, Medical University of Lodz, University Clinical Hospital No 2, Łodz, Poland

autor

Slominska E.

autor

Polakowska E.

autor

Mlynarski W.

autor

Watala C.

Bibliografia

• Bartus M, Lomnicka M, Kostogrys RB, Kazmierczak P, Watala C, Slominska EM, Smolenski RT, Pisulewski PM, Adamus J, Gebicki J, Chlopicki S (2008) 1-Methylnicotinamide (MNA) prevents endothelial dysfunction in hypertriglyceridemic and diabetic rats. Pharmacol Rep 60: 127-138. 
• Burkart V, Wang ZQ, Radons J, Heller B, Herceg Z, Stingl L, Wagner EF, Kolb H (1999) Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin. Nat Med 5: 314-319. 
• Chlopicki S, Swies J, Mogielnicki A, Buczko W, Bartus M, Lomnicka M, Adamus J, Gebicki J (2007) 1-Methylnicotinamide (MNA) a primary metabolite of nicotinamide exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway. Br J Pharmacol 152: 230-239. 
• Gebicki J, Sysa-Jedrzejowska A, Adamus J, Wozniacka A, Rybak M, Zielonka J (2003) 1-Methylnicotinamide: a potent anti-inflammatory agent of vitamin origin. Pol J Pharmacol 55: 109-112. 
• Hassan N, Janjua MZ (2001) The optimum dose of nicotinamide for protection of pancreatic beta-cells against the cytotoxic effect of streptozotocin in albino rat. J Ayub Med Coll Abbottabad 13: 26-30. 
• Hoorens A, Pipeleers D (1999) Nicotinamide protects human beta cells against chemically-induced necrosis but not against cytokine-induced apoptosis. Diabetologia 42: 55-59. 
• Masutani M, Suzuki H, Kamada N, Watanabe M, Ueda O, Nozaki T, Jishage K, Watanabe T, Sugimoto T, Nakagama H, Ochiya T, Sugimura T (1999) Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes. Proc Natl Acad Sci USA 96: 2301-2304. 
• Pieper AA, Brat DJ, Krug DK, Watkins CC, Gupta A, Blackshaw S, Verma A, Wang ZQ, Snyder SH (1999) Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes. Proc Natl Acad Sci USA 96: 3059-3064. 
• Przygodzki T, Kazmierczak P, Sikora J, Watala C (2010) 1-methylnicotinamide effects on the selected markers of endothelial function inflammation and haemostasis in diabetic rats. Eur J Pharmacol 640: 157-162. 
• Slominska EM, Yuen A, Osman L, Gebicki J, Yacoub MH, Smolenski RT (2008) Cytoprotective effects of nicotinamide derivatives in endothelial cells. Nucleosides Nucleotides Nucleic Acids 27: 863-866. 
• Smolenski RT, Lachno DR, Ledingham SJ, Yacoub MH (1990) Determination of sixteen nucleotides nucleosides and bases using high-performance liquid chromatography and its application to the study of purine metabolism in hearts for transplantation. J Chromatogr 527: 414-420. 
• Uchigata Y, Yamamoto H, Kawamura A, Okamoto H (1982) Protection by superoxide dismutase catalase and poly(ADP-ribose) synthetase inhibitors against alloxan- and streptozotocin-induced islet DNA strand breaks and against the inhibition of proinsulin synthesis. J Biol Chem 257: 6084-6088. 
• Watala C, Kazmierczak P, Dobaczewski M, Przygodzki T, Bartus M, Lomnicka M, Slominska EM, Durackova Z, Chlopicki S (2009) Anti-diabetic effects of 1-methylnicotinamide (MNA) in streptozocin-induced diabetes in rats. Pharmacol Rep 61: 86-98. 
• Wozniacka A, Wieczorkowska M, Gebicki J, Sysa-Jedrzejowska A (2005) Topical application of 1-methylnicotinamide in the treatment of rosacea: a pilot study. Clin Exp Dermatol 30: 632-635.