Abstract
Methylglyoxal (MG), a highly reactive α-oxoaldehyde generated by oxidation of carbohydrate and glycolysis, binds to proteins and forms advanced glycation end products (AGE). MG and MG adducts have been implicated in oxidative stress-related diseases, therefore, MG detoxifying system such as the glyoxalase system (glyoxalase I) also contributes to progression of these diseases. Recent papers have emphasized the pathophysiological effects of MG and the glyoxalase system in acute hypoxic injury, which is associated with acute oxidative stress. We investigated the kinetics of MG level and glyoxalase I activity in renal acute hypoxic injury induced by ischemia-reperfusion (I/R). I/R induced tubulointerstitial injury and the histological changes were associated with a significant decrease in renal glyoxalase I activity and an increase in MG level in the damaged tubular cells. Of note, rats over expressing human glyoxalase I showed amelioration of I/R-induced histological and functional damages and it was associated with a decrease in MG level in the lesion resulting in reduction of oxidative stress and tubular cell apoptosis. In conclusion, glyoxalase I has renoprotective effects in renal hypoxia such as I/R injury via a reduction in cytotoxic MG level in tubular cells.
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References
Nangaku M (2006) Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure. J Am Soc Nephrol 17:17–25.
Matsumoto M, Makino Y, Tanaka T et al. (2003) Induction of renoprotective gene expression by cobalt ameliorates ischemic injury of the kidney in rats. J Am Soc Nephrol 14:1825–1832.
Ohtomo S, Nangaku M, Izuhara Y et al. (2008) Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model. Nephrol Dial Transplant 23:1166–1172.
Kojima I, Tanaka T, Inagi R et al. (2007) Protective role of hypoxia-inducible factor-2alpha against ischemic damage and oxidative stress in the kidney. J Am Soc Nephrol 18:1218–1226.
Makino Y, Cao R, Svensson K et al. (2001) Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 414:550–554.
Biswas S, Ray M, Misra S et al. (1997) Selective inhibition of mitochondrial respiration and glycolysis in human leukaemic leucocytes by methylglyoxal. Biochem J 323:343–348.
de Arriba SG, Stuchbury G, Yarin J et al. (2007) Methylglyoxal impairs glucose metabolism and leads to energy depletion in neuronal cells. Neurobiol Aging 28:1044–1050.
Halder J, Ray M, Ray S (1993) Inhibition of glycolysis and mitochondrial respiration of Ehrlich ascites carcinoma cells by methylglyoxal. Int J Can-cer 54:443–449.
Chan WH, Wu HJ, Shiao NH (2007) Apoptotic signaling in methylglyoxal-treated human osteoblasts involves oxidative stress, c-Jun N-terminal kinase, caspase-3, and p21-activated kinase 2. J Cell Biochem 100:1056–1069.
Godbout JP, Pesavento J, Hartman ME et al. (2002) Methylglyoxal enhances cisplatin-induced cytotoxicity by activating protein kinase C delta. J Biol Chem 277:2554–2561.
Chan WH, Wu HJ (2008) Methylglyoxal and high glucose co-treatment induces apoptosis or necrosis in human umbilical vein endothelial cells. J Cell Biochem 103:1144–1157.
Oya T, Hattori N, Mizuno Y et al. (1999) Methylglyoxal modification of protein. Chemical and immunochemical characterization of methylglyoxal-arginine adducts. J Biol Chem 274:18492–18502.
Bucciarelli LG, Kaneko M, Ananthakrishnan R et al. (2006) Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury. Circulation 113:1226–34.
Thornalley PJ (2003) Glyoxalase I–structure, function and a critical role in the enzymatic defence against glycation. Biochem Soc Trans 31:1343–1348 Review.
Miyata T, van Ypersele de Strihou C, Imasawa T et al. (2001) Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient. Kidney Int 60:2351–1359.
Barati MT, Merchant ML, Kain AB et al. (2007) Proteomic analysis defines altered cellular redox pathways and advanced glycation end-product metabolism in glomeruli of db/db diabetic mice. Am J Physiol Renal Physiol 293:F1157–F1165.
Shinohara M, Thornalley PJ, Giardino I et al. (1998) Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J Clin Invest 101:1142–1147.
Morcos M, Du X, Pfisterer F et al. (2008) Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. Aging Cell 7:260–269.
Creighton DJ, Zheng ZB, Holewinski R et al. (2003) Glyoxalase I inhibitors in cancer chemotherapy. Biochem Soc Trans 31:1378–1382 Review.
Kumagai T, Nangaku M, Kojima I et al. (2008) Glyoxlase I overexpression ameliorates renal ischemia-reperfusion injury in rats. Am J Physiol Renal Physiol 296(4):F912–F921.
Inagi R, Miyata T, Ueda Y et al. (2002) Efficient in vitro lowering of carbonyl stress by the glyoxalase system in conventional glucose peritoneal dialysis fluid. Kidney Int 62:679–87.
Ceradini DJ, Yao D, Grogan RH et al. (2008) Decreasing intracellular superoxide corrects defective ischemia-induced new vessel formation in diabetic mice. J Biol Chem 283:10930–10938.
Acknowledgments
This work was supported by Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (19590939 to RI and 19390228 to MN).
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Inagi, R., Kumagai, T., Fujita, T., Nangaku, M. (2010). The Role of Glyoxalase System in Renal Hypoxia. In: Takahashi, E., Bruley, D. (eds) Oxygen Transport to Tissue XXXI. Advances in Experimental Medicine and Biology, vol 662. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1241-1_6
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DOI: https://doi.org/10.1007/978-1-4419-1241-1_6
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