title: Antioxidants inhibit advanced glycosylation end-product-induced apoptosis by downregulation of miR-223 in human adipose tissue-derived stem cells.
abstract: Advanced glycosylation end products (AGEs) are endogenous inflammatory mediators that induce apoptosis of mesenchymal stem cells. A potential mechanism includes increased generation of reactive oxygen species (ROS). MicroRNA-223 (miR-223) is implicated in the regulation of cell growth and apoptosis in several cell types. Here, we tested the hypothesis that antioxidants N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) inhibit AGE-induced apoptosis via a microRNA-dependent mechanism in human adipose tissue-derived stem cells (ADSCs). Results showed that AGE-HSA enhanced apoptosis and caspase-3 activity in ADSCs. AGE-HSA also increased ROS generation and upregulated the expression of miR-223. Interestingly, reductions in ROS generation and apoptosis, and upregulation of miR-223 were found in ADSCs treated with antioxidants NAC and AAP. Furthermore, miR-223 mimics blocked antioxidant inhibition of AGE-induced apoptosis and ROS generation. Knockdown of miR-223 amplified the protective effects of antioxidants on apoptosis induced by AGE-HSA. miR-223 acted by targeting fibroblast growth factor receptor 2. These results indicate that NAC and AAP suppress AGE-HSA-induced apoptosis of ADSCs, possibly through downregulation of miR-223.
authors.affiliation: Department of Blood Transfusion, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Central Hospital of Shenyang Medical College, Shenyang 110024, China.
authors.forename: Hongqiu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Blood Transfusion, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health, China medical University, Shenyang 110001, China.
authors.forename: Dianbao
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects; D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D053148:Caspase 3 / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000008:administration & dosage; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000008:administration & dosage; D000075462:Serum Albumin, Human
chemical_list: D000111:Acetylcysteine; D000975:Antioxidants; D001205:Ascorbic Acid; D053148:Caspase 3; D017127:Glycation End Products, Advanced; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D000075462:Serum Albumin, Human; C525067:MIR223, human; C109748:advanced glycation end products-human serum albumin; C011669:ascorbate-2-phosphate