title: Aluminum oxide nanoparticles alter cell cycle progression through CCND1 and EGR1 gene expression in human mesenchymal stem cells.
abstract: Aluminum oxide nanoparticles (Al2 O3 -NPs) are important ceramic materials that have been used in a variety of commercial and industrial applications. However, the impact of acute and chronic exposure to Al2 O3 -NPs on the environment and on human health has not been well studied. In this investigation, we evaluated the cytotoxic effects of Al2 O3 -NPs on human mesenchymal stem cells (hMSCs) by using a cell viability assay and observing cellular morphological changes, analyzing cell cycle progression, and monitoring the expression of cell cycle response genes (PCNA, EGR1, E2F1, CCND1, CCNC, CCNG1, and CYCD3). The Al2 O3 -NPs reduced hMSC viability in a dose- and time-dependent manner. Nuclear condensation and fragmentation, chromosomal DNA fragmentation, and cytoplasmic vacuolization were observed in Al2 O3 -NP-exposed cells. The nuclear morphological changes indicated that Al2 O3 -NPs alter cell cycle progression and gene expression. The cell cycle distribution revealed that Al2 O3 -NPs cause cell cycle arrest in the sub-G0-G1 phase, and this is associated with a reduction in the cell population in the G2/M and G0/G1 phases. Moreover, Al2 O3 -NPs induced the upregulation of cell cycle response genes, including EGR1, E2F1, and CCND1. Our results suggested that exposure to Al2 O3 -NPs could cause acute cytotoxic effects in hMSCs through cell cycle regulatory genes.
authors.affiliation: Nanobiotechnology and Molecular Biology Research Laboratory, Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Vaiyapuri Subbarayan
authors.initials: VS
authors.lastname: Periasamy
authors.affiliation: Nanobiotechnology and Molecular Biology Research Laboratory, Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Jegan
authors.initials: J
authors.lastname: Athinarayanan
authors.affiliation: Nanobiotechnology and Molecular Biology Research Laboratory, Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Alshatwi
mesh_terms: D000537:Aluminum Oxide / Q000737:chemistry / Q000633:toxicity*; D001692:Biological Transport / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics*; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D015415:Biomarkers; C530104:CCND1 protein, human; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D019938:Cyclin D1; D000537:Aluminum Oxide
keywords: Al2O3 nanoparticles; cell cycle; cell death; gene expression; mesenchymal stem cells