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20. Antichagasic Activity of Komaroviquinone Is Due to Generation of Reactive Oxygen Species Catalyzed by Trypanosoma cruzi Old Yellow Enzyme

Author

Uchiyama, Nahoko, primary, Kabututu, Zakayi, additional, Kubata, Bruno K., additional, Kiuchi, Fumiyuki, additional, Ito, Michiho, additional, Nakajima-Shimada, Junko, additional, Aoki, Takashi, additional, Ohkubo, Kei, additional, Fukuzumi, Shunichi, additional, Martin, Samuel K., additional, Honda, Gisho, additional, and Urade, Yoshihiro, additional

Published
2005
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49. Coagulation in the mesangial area promotes ECM accumulation through factor V expression in MsPGN in rats.

Author

Liu, Ning, Makino, Toshiaki, Nogaki, Fumiaki, Kusano, Hitoshi, Suyama, Katsuo, Muso, Eri, Honda, Gisho, Kita, Toru, and Ono, Takahiko

Subjects
GLOMERULONEPHRITIS, EXTRACELLULAR matrix, TRANSFORMING growth factors-beta, CONNECTIVE tissue development, GROWTH factors, PHYSIOLOGY
Abstract

It is well known that tissue factor starts the extrinsic coagulation pathway, which activates factor X to Xa, and factor V is a membrane-bound potent cofactor for the terminating stage of prothrombin activation by factor Xa. In a previous in vitro study, factor V was induced in cultured mesangial cells by inflammatory stimulation and increased expression of factor V promoted fibrin generation on the cultured mesangial cell surface. We report that extracellular matrix (ECM) accumulation is increased in association with coagulation in the mesangial area through factor V expression in mesangioproliferative glomerulonephritis (MsPGN). Wistar rats were intravenously injected with rabbit anti-rat thymocyte serum accompanied with or without simultaneous injection of rabbit anti-factor V antibody. Time course study in immunohistochemistry revealed that factor V expression was prominent on day 3 and fibrin-related antigen (FRA) deposition, then ECM accumulation, followed from day 3 to day 8. Massive fibronectin depositions and transforming growth factor (TGF)-β expression were also noted in glomeruli from the disease control group, markedly higher than those in the normal group, and these depositions and expressions were significantly decreased in the anti-factor V neutralizing antibodyinjected group. Northern blot analysis revealed that factor V mRNA expression was prominent on day 3 and was weak on day 8. Doublelabeling experiments revealed the frequent colocalization of α-smooth muscle actin with factor V, FRA, and fibronectin in the same mesangial areas of glomeruli. TGF-β, connective tissue growth factor (CTGF), collagen type IV, and fibronectin mRNA were upregulated in the disease control group, and anti-factor V-neutralizing antibody injection suppressed these mRNA expressions in glomeruli. The present results suggest that ECM components accumulation may progress in accordance with coagulation in the mesangial area through mesangial factor V expression and upregulated expression of TGF-β and CTGF in MsPGN. [ABSTRACT FROM AUTHOR]

Published
2004
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50. Antichagasic Activity of Komaroviquinone Is Due to Generation of Reactive Oxygen Species Catalyzed by Trypanosoma cruziOld Yellow Enzyme

Author

Uchiyama, Nahoko, Kabututu, Zakayi, Kubata, Bruno K., Kiuchi, Fumiyuki, Ito, Michiho, Nakajima-Shimada, Junko, Aoki, Takashi, Ohkubo, Kei, Fukuzumi, Shunichi, Martin, Samuel K., Honda, Gisho, and Urade, Yoshihiro

Abstract

ABSTRACTA novel potent trypanocidal diterpene, komaroviquinone, was reduced by Trypanosoma cruziold yellow enzyme (TcOYE) to its semiquinone radical. The reductase activity in trypanosome lysates was completely immunoabsorbed by anti-TcOYE antibody. Since TcOYE is expressed throughout the T. cruzilife cycle, komaroviquinone is an interesting candidate for developing new antichagasic drugs.

Published
2005
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