Author(s): Deshpande SB, Hida H, Takei-Io N, Masuda T, Baba H, et al.
The roles of nitric oxide (NO) in 3-nitropropionic acid (3-NPA)-induced toxicity were investigated using in vivo and in vitro models. Chronic 3-NPA administration (10 mg/kg) to rats produced selective striatal lesions that were associated with abnormal motor and EMG activities. In these animals, there was loss of glial fibrillary acidic protein (GFAP)-positive cells with extravasation of IgG in the lesion center, although microtubule-associated protein (MAP)-2-positive cells remained, indicating that astrocytes were involved. 3-NPA increased the NO2−/NO3− levels in microdialysates obtained from the striatum, thalamus and cerebellum. The basal NO3− level was much higher in the striatum than in the other areas. The NO2−/NO3− levels in the striatum were much higher in animals exhibiting abnormal muscular activity. Expression of endothelial NO synthase (eNOS), but not neuronal NOS (nNOS), was greatly increased in the striatum at 5 h after a second 3-NPA exposure, but not in other areas. In astrocyte cultures, the toxic effects of 3-NPA were associated with corresponding increases in the NO2− level, and this toxicity was attenuated by hemoglobin (Hb; 20 μM), which quenches NO. The NO2− generated by 3-NPA, even without cells, was also antagonized by Hb. 3-NPA, S-nitroso-n-acetyl-dl-penicillamine (SNAP) and sodium nitroprusside (SNP) all increased the NO current (detected by NO-sensitive electrodes) in concentration-dependent manners, and Hb significantly attenuated the NO generation induced by 3-NPA, SNAP or SNP. Taken together, these results suggest that 3-NPA generates NO both directly as a donor and indirectly by enhancing NOS expression to produce toxic effects on astrocytes and neuronal toxicity.
Author(s): Pascoe MC, Howells DW, Crewther DP, Carey LM, Crewther SG, et al.
Author(s): Zhu H, Fan C, Xu F, Tian C, Zhang F, et al.
Author(s): Russell KL, Berman NEJ, Gregg PRA, Levant B
Author(s): Haraguchi T, Yanaka N, Eguchi Y, Kudo T, Hirata A, et al.
Author(s): Taepavarapruk P, Song C
Author(s): Gupta S, Sharma B
Author(s): Solesio ME, Saez-Atienzar S, Jordan J, Galindo MF
Author(s): Cho KJ, Kim HW, Cheon SY,Lee JE, Kim GW, et al.
Author(s): Shinomol GK, Bharath MMS, MuralidharaM
Author(s): Mahdy HM, Mohamed MR, Emam MA, Karim AM, Abdel-Naim A, et al.
Author(s): Tian C, Kim YH, Kim YC, Park KT, Kim SW, et al.
Author(s): Colle D, Santos DB, Hartwig JM, Godoi M, Engel DF, et al.
Author(s): Hashimoto M, Katakura M, Hossain S, Rahman A, Shimada T, et al.
Author(s): Luchtman DW, Song C
Author(s): Wu H, Ichikawa S, Tani C,Zhu B, Tada M, et al.
Author(s): Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, et al.
Author(s): Luchtman DW, Meng Q, Wang X, Shao D, Song C, et al.
Author(s): Denny Joseph KM, MuralidharaM
Author(s): Binawade Y, Jagtap A
Author(s): Moreadith RW, Fiskum G
Author(s): Ohkawa H, Ohishi N, Yagi K
Author(s): Wolff SP
Author(s): Levine RL, Garland D, Oliver CN, Amici A, Climent I, et al.
Author(s): Mokrasch LC, Teschke EJ
Author(s): Kostyuk VA, Potapovich AI
Author(s): Aebi H
Author(s): Luthman M, Holmgren A
Author(s): Guthenberg C, Alin P, Mannervik B
Author(s): Flohé L, Günzler WA
Author(s): Ellman GL, Courtney KD, Andres V, Feather-Stone RM
Author(s): Dalpiaz A, Filosa R, de Caprariis P, Conte G, BortolottiF, et al.
Author(s): Pennington RJ
Author(s): Navarro A, Gomez C, López-Cepero JM, Boveris A
Author(s): Lowry OH, Rosebrough NJ, Farr AL, Randall RJ
Author(s): Kidd PM
Author(s): Kou W, Luchtman D, Song C
Author(s): Véricel E, Polette A, Bacot S, Calzada C, Lagarde M, et al.
Author(s): Herrera-Mundo N, Sitges M
Author(s): Singh S, Misiak M, Beyer C, Arnold S
Author(s): Dalle-Donne I, Scaloni A, Giustarini D,Cavarra E, Tell G, et al.
Author(s): Stadtman ER
Author(s): Méndez L, Pazos M, Gallardo JM, Torres JL, Pérez-JiménezJ, et al.
Author(s): Kumar P, Kumar A
Author(s): Lu SC
Author(s): Halliwell B
Author(s): Smith R, Chung H, Rundquist S, Maat-Schieman ML, Colgan L, et al.
Author(s): Girish C, MuralidharaM
Author(s): Prasad SN, MuralidharaM
Author(s): Bhutada P, Mundhada Y, Bansod K, Tawari S, Patil S, et al.
Author(s): Park JE, Lee ST, Im WS,Chu K, Kim M,et al.
Author(s): Al Mutairy A, Al Kadasah S, Elfaki I,Arshaduddin M, Malik D, et al.
Author(s): Nishino H, Kumazaki M, Fukuda A,Fujimoto I, Shimano Y, et al.