title: Oxidative stress inhibits adhesion and transendothelial migration, and induces apoptosis and senescence of induced pluripotent stem cells.
abstract: Oxidative stress caused by cellular accumulation of reactive oxygen species (ROS) is a major contributor to disease and cell death. However, how induced pluripotent stem cells (iPSC) respond to different levels of oxidative stress is largely unknown. Here, we investigated the effect of H2 O2 -induced oxidative stress on iPSC function in vitro. Mouse iPSC were treated with H2 O2 (25-100 μmol/L). IPSC adhesion, migration, viability, apoptosis and senescence were analysed. Expression of adhesion-related genes, stress defence genes, and osteoblast- and adipocyte-associated genes were determined by reverse transcription polymerase chain reaction. The present study found that H2 O2 (25-100 μmol/L) decreased iPSC adhesion to matrix proteins and endothelial cells, and downregulated gene expression levels of adhesion-related molecules, such as integrin alpha 7, cadherin 1 and 5, melanoma cell adhesion molecule, vascular cell adhesion molecule 1, and monocyte chemoattractant protein-1. H2 O2 (100 μmol/L) decreased iPSC viability and inhibited the capacity of iPSC migration and transendothelial migration. iPSC were sensitive to H2 O2 -induced G2/M arrest, senescence and apoptosis when exposed to H2 O2 at concentrations above 25 μmol/L. H2 O2 increased the expression of stress defence genes, including catalase, cytochrome B alpha, lactoperoxidase and thioredoxin domain containing 2. H2 O2 upregulated the expression of osteoblast- and adipocyte-associated genes in iPSC during their differentiation; however, short-term H2 O2 -induced oxidative stress did not affect the protein expression of the pluripotency markers, octamer-binding transcription factor 4 and sex-determining region Y-box 2. The present results suggest that iPSC are sensitive to H2 O2 toxicity, and inhibition of oxidative stress might be a strategy for improving their functions.
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.forename: Xueqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Xueling
authors.initials: X
authors.lastname: Kang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Tiantian
authors.initials: T
authors.lastname: Hu
authors.forename: Meng
authors.initials: M
authors.lastname: Xiang
authors.forename: Xinhong
authors.initials: X
authors.lastname: Wang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yuan
authors.forename: Alex
authors.initials: A
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Meng
authors.forename: Sifeng
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules
keywords: cell adhesion; cell apoptosis; cell migration; cell senescence; induced pluripotent stem cell; oxidative stress