title: Aging-related kidney damage is associated with a decrease in klotho expression and an increase in superoxide production.
abstract: The purpose of this study was to determine changes in klotho, endothelin (ET) receptors, and superoxide production in kidneys of aged rats and whether these changes are exacerbated in aged rats with cognitive impairment. Twenty aged rats (male, 27 months) were divided into an Old Impaired group (n=9) and an Old Intact group (n=11) according to a cognitive function test. A group of 12-month-old rats (n=10) was used as a Young Intact group. Serum creatinine was increased significantly in the Old Impaired group, suggesting impaired renal function. Aged rats showed glomerulosclerosis and tubulointerstitialfibrosis. These pathological changes were markedly aggravated in the old cognitively impaired than in the old cognitively intact animals. Notably, aged rats demonstrated a significant decrease in klotho protein expression in renal cortex and medulla. Protein expression of IL-6, Nox2, ETa receptors and superoxide production were increased whereas mitochondrial SOD (MnSOD) and ETb receptors expression were decreased in kidneys of the aged rats. Interestingly, these changes were more pronounced in the old impaired than in the old intact rats. In conclusion, the aging-related kidney damage was exacerbated in aged rats with cognitive impairment. Klotho, ETB, and MnSOD were downregulated but ETa, IL-6, Nox2, and superoxide production were upregulated in the aging-related kidney damage. These changes were more pronounced in rats with cognitive impairment.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zuo
authors.forename: Han
authors.initials: H
authors.lastname: Lei
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Wang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wang
authors.forename: William
authors.initials: W
authors.lastname: Sonntag
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D003072:Cognition Disorders / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D005966:Glucuronidase / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000090265:Klotho Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis; D051381:Rats; D017466:Receptors, Endothelin / Q000096:biosynthesis*; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D008562:Membrane Glycoproteins; D017466:Receptors, Endothelin; D013481:Superoxides; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D005966:Glucuronidase; D000090265:Klotho Proteins