Rrm2b deletion causes mitochondrial metabolic defects in renal tubules

被引：11

作者：

Chen, Yi-Fan ^{[1
]}

Lin, I-Hsuan ^{[2
]}

Guo, Yu-Ru ^{[3
]}

Chiu, Wei-Jun ^{[1
]}

Wu, Mai-Szu ^{[4
,5
]}

Jia, Wei ^{[6
]}

Yen, Yun ^{[2
,3
]}

机构：

[1] Taipei Med Univ, Coll Med Sci & Technol, PhD Program ForTranslat Med, Taipei 11031, Taiwan

[2] Taipei Med Univ, TMU Res Ctr Canc Translat Med, Taipei 11031, Taiwan

[3] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei 11031, Taiwan

[4] Taipei Med Univ, Coll Med, Sch Med, Dept Internal Med, Taipei 11031, Taiwan

[5] Taipei Med Univ, Dept Internal Med, Div Nephrol, Shuang Ho Hosp, New Taipei 23561, Taiwan

[6] Univ Hawaii, Canc Ctr, Canc Biol Program, Honolulu, HI 96813 USA

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

HUMAN RIBONUCLEOTIDE REDUCTASE; DEVELOPING KIDNEY; REDOX PROPERTY; RAT-LIVER; P53R2; GENE; FAILURE; CANCER; REPAIR; CELLS;

D O I：

10.1038/s41598-019-49663-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Renal diseases impose considerable health and economic burdens on health systems worldwide, and there is a lack of efficient methods for the prevention and treatment due to their complexity and heterogeneity. Kidneys are organs with a high demand for energy produced by mitochondria, in which Rrm2b has critical functions as reported. The Rrm2b kidney-specific knockout mice we generated exhibited age-dependent exacerbated features, including mitochondria! dysfunction and increased oxidative stress; additionally, resulted in severe disruption of mitochondria-related metabolism. Rrm2b is vital not only to supply dNTPs for DNA replication and repair, but also to maintain structural integrity and metabolic homeostasis in mitochondria. Thence, Rrm2b deletion might induce chronic kidney defects in mice. This model can facilitate exploration of novel mechanisms and targeted therapies in the kidney diseases and has important translational and clinical implications.

引用

页数：12

共 38 条

[1] Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion [J].

Bourdon, Alice ;

Minai, Limor ;

Serre, Valerie ;

Jais, Jean-Philippe ;

Sarzi, Emmanuelle ;

Aubert, Sophie ;

Chretien, Dominique ;

de Lonlay, Pascale ;

Paquis-Flucklinger, Veronique ;

Arakawa, Hirofumi ;

Nakamura, Yusuke ;

Munnich, Arnold ;

Rotig, Agnes .

NATURE GENETICS, 2007, 39 (06) :776-780

[2] Aldehyde Dehydrogenase 7A1 (ALDH7A1) Is a Novel Enzyme Involved in Cellular Defense against Hyperosmotic Stress [J].

Brocker, Chad ;

Lassen, Natalie ;

Estey, Tia ;

Pappa, Aglaia ;

Cantore, Miriam ;

Orlova, Valeria V. ;

Chavakis, Triantafyllos ;

Kavanagh, Kathryn L. ;

Oppermann, Udo ;

Vasiliou, Vasilis .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (24) :18452-18463

[3] Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice [J].

Chen, Yi-Fan ;

Kao, Cheng-Heng ;

Chen, Ya-Ting ;

Wang, Chih-Hao ;

Wu, Chia-Yu ;

Tsai, Ching-Yen ;

Liu, Fu-Chin ;

Yang, Chu-Wen ;

Wei, Yau-Huei ;

Hsu, Ming-Ta ;

Tsai, Shih-Feng ;

Tsai, Ting-Fen .

GENES & DEVELOPMENT, 2009, 23 (10) :1183-1194

[4] Immunohistochemical detection of betaine-homocysteine S-methyltransferase in human, pig, and rat liver and kidney [J].

Delgado-Reyes, CV ;

Wallig, MA ;

Garrow, TA .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2001, 393 (01) :184-186

[5] Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors [J].

Fordahl, Steve ;

Cooney, Paula ;

Qiu, Yunping ;

Xie, Guoxiang ;

Jia, Wei ;

Erikson, Keith M. .

NEUROTOXICOLOGY AND TERATOLOGY, 2012, 34 (01) :27-36

[6] Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies [J].

Haque, Syed K. ;

Ariceta, Gema ;

Batlle, Daniel .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2012, 27 (12) :4273-4287

[7] High homocysteine induces betaine depletion [J].

Imbard, Apolline ;

Benoist, Jean-Francois ;

Esse, Ruben ;

Gupta, Sapna ;

Lebon, Sophie ;

de Vriese, An S. ;

de Baulny, Helene Ogier ;

Kruger, Warren ;

Schiff, Manuel ;

Blom, Henk J. .

BIOSCIENCE REPORTS, 2015, 35

[8] High-throughput data analysis for detecting and identifying differences between samples in GC/MS-based metabolomic analyses [J].

Jonsson, P ;

Johansson, AI ;

Gullberg, J ;

Trygg, J ;

A, J ;

Grung, B ;

Marklund, S ;

Sjoström, M ;

Antti, H ;

Moritz, T .

ANALYTICAL CHEMISTRY, 2005, 77 (17) :5635-5642

[9] The critical role of catalase in prooxidant and antioxidant function of p53 [J].

Kang, M. Y. ;

Kim, H-B ;

Piao, C. ;

Lee, K. H. ;

Hyun, J. W. ;

Chang, I-Y ;

You, H. J. .

CELL DEATH AND DIFFERENTIATION, 2013, 20 (01) :117-129

[10] Impaired function of p53R2 in Rrm2b-null mice causes severe renal failure through attenuation of dNTP pools [J].

Kimura, T ;

Takeda, S ;

Sagiya, Y ;

Gotoh, M ;

Nakamura, Y ;

Arakawa, H .

NATURE GENETICS, 2003, 34 (04) :440-445

← 1 2 3 4 →