title: MitoTEMPO Prevents Oxalate Induced Injury in NRK-52E Cells via Inhibiting Mitochondrial Dysfunction and Modulating Oxidative Stress.
abstract: As one of the major risks for urolithiasis, hyperoxaluria can be caused by genetic defect or dietary intake. And high oxalate induced renal epithelial cells injury is related to oxidative stress and mitochondrial dysfunction. Here, we investigated whether MitoTEMPO, a mitochondria-targeted antioxidant, could protect against oxalate mediated injury in NRK-52E cells via inhibiting mitochondrial dysfunction and modulating oxidative stress. MitoSOX Red was used to determine mitochondrial ROS (mtROS) production. Mitochondrial membrane potential (Δψm) and quantification of ATP synthesis were measured to evaluate mitochondrial function. The protein expression of Nox4, Nox2, and p22 was also detected to explore the effect of oxalate and MitoTEMPO on NADPH oxidase. Our results revealed that pretreatment with MitoTEMPO significantly inhibited oxalate induced lactate dehydrogenase (LDH) and malondialdehyde (MDA) release and decreased oxalate induced mtROS generation. Further, MitoTEMPO pretreatment restored disruption of Δψm and decreased ATP synthesis mediated by oxalate. In addition, MitoTEMPO altered the protein expression of Nox4 and p22 and decreased the protein expression of IL-6 and osteopontin (OPN) induced by oxalate. We concluded that MitoTEMPO may be a new candidate to protect against oxalate induced kidney injury as well as urolithiasis.
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jiaqiao
authors.identifier: 0000-0001-6747-0654
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qing
authors.identifier: 0000-0002-2982-0147
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Chuou
authors.identifier: 0000-0002-2346-3150
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yuchao
authors.identifier: 0000-0003-4523-2342
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Henglong
authors.identifier: 0000-0002-3618-7036
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Baolong
authors.identifier: 0000-0001-8886-8960
authors.initials: B
authors.lastname: Qin
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yufeng
authors.identifier: 0000-0001-8306-5368
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Deng
authors.identifier: 0000-0002-1669-1729
authors.initials: D
authors.lastname: He
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Cong
authors.identifier: 0000-0001-6986-629X
authors.initials: C
authors.lastname: Li
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Shaogang
authors.identifier: 0000-0002-3206-1495
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D005434:Flow Cytometry; D007684:Kidney Tubules / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010070:Oxalates / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; C555916:MitoTEMPO; D009943:Organophosphorus Compounds; D010070:Oxalates; D010880:Piperidines; D017382:Reactive Oxygen Species