Novel effect of the inhibitor of mitochondrial cyclophilin D activation,N-methyl-4-isoleucine cyclosporin, on renal calcium crystallization

作者: Kazuhiro Niimi , Takahiro Yasui , Atsushi Okada , Yasuhiko Hirose , Yasue Kubota

DOI: 10.1111/IJU.12425

关键词:

摘要: Objectives To experimentally evaluate the clinical application of N-methyl-4-isoleucine cyclosporin, a novel selective inhibitor cyclophilin D activation. Methods In vitro, cultured renal tubular cells were exposed to calcium oxalate monohydrate crystals and treated with cyclosporin. The mitochondrial membrane was stained tetramethylrhodamine ethyl ester perchlorate observed. In vivo, Sprague–Dawley rats divided into four groups: control group, an ethylene glycol group (administration induce crystallization), cyclosporin cyclosporin) glycol + N-methyl-4-isoleucine cyclosporin). Renal crystallization evaluated using Pizzolato staining. Oxidative stress superoxide dismutase 8-hydroxy-deoxyguanosine. Mitochondria within observed by transmission electron microscopy. Cell apoptosis cleaved caspase-3. Results In vitro, induced depolarization potential, which remarkably prevented administration crystallization, oxidative stress, collapse cell in rats, significantly cyclosporin. Conclusions Herein we first report new treatment agent determining through activation.

参考文章(29)
K. Kohri, S. Nomura, Y. Kitamura, T. Nagata, K. Yoshioka, M. Iguchi, T. Yamate, T. Umekawa, Y. Suzuki, H. Sinohara, Structure and expression of the mRNA encoding urinary stone protein (osteopontin). Journal of Biological Chemistry. ,vol. 268, pp. 15180- 15184 ,(1993) , 10.1016/S0021-9258(18)82453-X
Gary C. Curhan, Epidemiology of Stone Disease Urologic Clinics of North America. ,vol. 34, pp. 287- 293 ,(2007) , 10.1016/J.UCL.2007.04.003
Heng Du, Lan Guo, Fang Fang, Doris Chen, Alexander A Sosunov, Guy M McKhann, Yilin Yan, Chunyu Wang, Hong Zhang, Jeffery D Molkentin, Frank J Gunn-Moore, Jean Paul Vonsattel, Ottavio Arancio, John Xi Chen, Shi Du Yan, Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease Nature Medicine. ,vol. 14, pp. 1097- 1105 ,(2008) , 10.1038/NM.1868
Peter C Waldmeier, William G Tatton, Interrupting apoptosis in neurodegenerative disease: potential for effective therapy? Drug Discovery Today. ,vol. 9, pp. 210- 218 ,(2004) , 10.1016/S1359-6446(03)03000-9
Masahito Hirose, Keiichi Tozawa, Atsushi Okada, Shuzo Hamamoto, Yuji Higashibata, Bin Gao, Yutaro Hayashi, Hideo Shimizu, Yasue Kubota, Takahiro Yasui, Kenjiro Kohri, Role of osteopontin in early phase of renal crystal formation: immunohistochemical and microstructural comparisons with osteopontin knock-out mice Urological Research. ,vol. 40, pp. 121- 129 ,(2012) , 10.1007/S00240-011-0400-Z
Christopher P. Baines, The molecular composition of the mitochondrial permeability transition pore. Journal of Molecular and Cellular Cardiology. ,vol. 46, pp. 850- 857 ,(2009) , 10.1016/J.YJMCC.2009.02.007
Lu-Cheng Cao, Thomas W. Honeyman, Rachel Cooney, Lori Kennington, Cheryl R. Scheid, Julie A. Jonassen, Mitochondrial dysfunction is a primary event in renal cell oxalate toxicity. Kidney International. ,vol. 66, pp. 1890- 1900 ,(2004) , 10.1111/J.1523-1755.2004.00963.X
Hyo-Jung Lee, Soo-Jin Jeong, Hyo-Jeong Lee, Eun-Ok Lee, Hyunsu Bae, John C. Lieske, Sung-Hoon Kim, 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose reduces renal crystallization and oxidative stress in a hyperoxaluric rat model Kidney International. ,vol. 79, pp. 538- 545 ,(2011) , 10.1038/KI.2010.458
Kazuhiro Niimi, Takahiro Yasui, Masahito Hirose, Shuzo Hamamoto, Yasunori Itoh, Atsushi Okada, Yasue Kubota, Yoshiyuki Kojima, Keiichi Tozawa, Shoichi Sasaki, Yutaro Hayashi, Kenjiro Kohri, Mitochondrial permeability transition pore opening induces the initial process of renal calcium crystallization. Free Radical Biology and Medicine. ,vol. 52, pp. 1207- 1217 ,(2012) , 10.1016/J.FREERADBIOMED.2012.01.005
Atsushi Okada, Shintaro Nomura, Yukihiko Saeki, Yuji Higashibata, Shuzo Hamamoto, Masahito Hirose, Yasunori Itoh, Takahiro Yasui, Keiichi Tozawa, Kenjiro Kohri, Morphological conversion of calcium oxalate crystals into stones is regulated by osteopontin in mouse kidney. Journal of Bone and Mineral Research. ,vol. 23, pp. 1629- 1637 ,(2008) , 10.1359/JBMR.080514