title: Hyperhomocysteinemia Exacerbates Cisplatin-induced Acute Kidney Injury.
abstract: Hyperhomocysteinemia (HHcy) has been linked to several clinical manifestations including chronic kidney disease. However, it is not known whether HHcy has a role in the development of acute kidney injury (AKI). In the present study, we reported that HHcy mice developed more severe renal injury after cisplatin injection and ischemia-reperfusion injury shown as more severe renal tubular damage and higher serum creatinine. In response to cisplatin, HHcy mice showed more prevalent tubular cell apoptosis and decreased tubular cell proliferation. Mechanistically, a heightened ER stress and a reduced Akt activity were observed in kidney tissues of HHcy mice after cisplatin injection. Stimulating cultured NRK-52E cells with Hcy significantly increased the fraction of cells in G2/M phase and cell apoptosis together with decreased Akt kinase activity. Akt agonist IGF-1 rescued HHcy-induced cell cycle arrest and cell apoptosis. In conclusion, the present study provides evidence that HHcy increases the sensitivity and severity of AKI.
authors.affiliation: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China;; Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guiyang, P.R. China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Long
authors.affiliation: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhen
authors.affiliation: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Fengxin
authors.initials: F
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guiyang, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zha
authors.affiliation: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats
chemical_list: D006710:Homocysteine; D002945:Cisplatin
keywords: AKI; ER stress.; Hyperhomocysteinemia; apoptosis; cell proliferation