title: Zinc transporter 5 and zinc transporter 7 induced by high glucose protects peritoneal mesothelial cells from undergoing apoptosis.
abstract: Zinc is an essential micronutrient and cytoprotectant involved in many types of apoptosis. The zinc transporter family SLC30A (ZnTs) is an important factor in the regulation of zinc homeostasis; however, its function in apoptosis in peritoneal mesothelial cells (PMCs) remains unknown. This study explores the regulation of zinc transporters and how they play a role in cell survival, particularly in rat peritoneal mesothelial cells (RPMCs), surrounding glucose concentrations, and the molecular mechanism involved. The messenger RNA (mRNA) transcripts were quantitatively measured by real-time polymerase chain reaction for all known nine zinc transport exporters (SLC30A1-8,10), as well as in primary RPMCs and the cells cultured under nonstimulated and HG-stimulated conditions. While many zinc transporters were constitutively expressed, ZnT5 mRNA and ZnT7 mRNA were strongly induced by HG. Overexpression of ZnT5 and ZnT7 respectively resulted in a decrease in the expression of caspace 3, caspace 8, BAX, and AIF and coincided with cell survival in the presence of HG. Inhibition of ZnT5 and ZnT7 expression using considerable siRNA-mediated knockdown of RPMCs was examined and, afterwards, the impact on cell apoptosis was investigated. Increased levels of apoptosis were observed after knockdown of ZnT5 and ZnT7. Furthermore, overexpression of ZnT5 and ZnT7 is accompanied by activation of PI3K/Akt pathway and inhibiting HG-induced apoptosis. This study suggests that the zinc transporting system in RPMCs is influenced by exposure to HG, particularly ZnT5 and ZnT7. This may account for the inhibition of HG-induced RPMC apoptosis and peritoneum injury, likely through targeting PI3K/Akt pathway-mediated cell survival.
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Liang
authors.forename: Baolei
authors.initials: B
authors.lastname: Guo
authors.forename: Wenyan
authors.initials: W
authors.lastname: Deng
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cai
authors.forename: Lining
authors.initials: L
authors.lastname: Wang
authors.forename: Jianfei
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology
chemical_list: D027682:Cation Transport Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C457225:SLC30A5 protein, human; C472294:SLC30A7 protein, human; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053181:Caspase 8; D005947:Glucose; D015032:Zinc