title: Nickel(II)-induced nasal epithelial toxicity and oxidative mitochondrial damage.
abstract: In probing the underlying mechanisms of nickel(II)-induced cytotoxicity on nasal epithelium, we investigated the effects of nickel(II) acetate on nasal epithelial RPMI-2650 cells. Nickel(II) elicited apoptosis, as signified by pyknotic and fragmented nuclei, increased caspase-3/7 activity, and an increase in annexin V binding, hypodiploid DNA, and Bax/Bcl-2 protein ratio. Nickel(II)-induced G2/M arrest was associated with up-regulation of p21(WAF1/CIP1) expression, decrease in phosphorylation at Thr(161) of Cdc2, and down-regulation of cyclin B1. Associated with these responses, ROS generation and mitochondrial depolarization increased in a nickel(II) concentration-dependent fashion. Pretreatment with N-acetylcysteine (NAC) attenuated these changes. p53 reporter gene assay and analyses of p53, Puma, Bax, and Bcl-2 protein levels indicated that NAC inhibited nickel(II)-induced activation of p53-mediated mitochondrial apoptotic pathway. Collectively, our study provides evidences that nickel(II) may induce oxidative damage on nasal epithelium in which antioxidant NAC protects cells against nickel(II)-induced apoptosis through the prevention of oxidative stress-mediated mitochondrial damage.
authors.affiliation: Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-930, Republic of Korea; Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 330-930, Republic of Korea.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-930, Republic of Korea.
authors.forename: Soo-Sung
authors.initials: SS
authors.lastname: Lim
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Cheonan 330-930, Republic of Korea.
authors.forename: Byoung Joon
authors.initials: BJ
authors.lastname: Baek
authors.affiliation: Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 330-930, Republic of Korea.
authors.forename: Je-Min
authors.initials: JM
authors.lastname: An
authors.affiliation: Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 330-930, Republic of Korea.
authors.forename: Hae-Seon
authors.initials: HS
authors.lastname: Nam
authors.affiliation: Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 330-930, Republic of Korea.
authors.forename: Kee-Min
authors.initials: KM
authors.lastname: Woo
authors.affiliation: Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 330-930, Republic of Korea.
authors.forename: Moon-Kyun
authors.initials: MK
authors.lastname: Cho
authors.affiliation: Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan 336-745, Republic of Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-930, Republic of Korea; Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 330-930, Republic of Korea. Electronic address: m1037624@sch.ac.kr.
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000111:Acetylcysteine; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation; D015386:Hazardous Substances / Q000633:toxicity*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000502:physiology; D009532:Nickel / Q000633:toxicity*; D018384:Oxidative Stress; D010766:Phosphorylation; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D017304:Annexin A5; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015386:Hazardous Substances; D009532:Nickel; D053148:Caspase 3; D000111:Acetylcysteine
keywords: Apoptosis; G2/M arrest; N-acetylcysteine; Nasal epithelium; Nickel(II) acetate; Oxidative damage