Aluminum oxide nanoparticles alter cell cycle progression through CCND1 and EGR1 gene expression in human mesenchymal stem cells

Journal Article
Alshatwi, Vaiyapuri Subbarayan Periasamy, Jegan Athinarayanan andAli A. . 2015
Publication Work Type
Ph.D
Magazine \ Newspaper
Biotechnology and Applied Biochemistry
Pages
10.1002/bab.1368
Publication Abstract

Aluminum oxide nanoparticles (Al2O3-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 Al2O3-NPs on the environment and on human health has not been well studied. In this investigation, we evaluated the cytotoxic effects of Al2O3-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 Al2O3-NPs reduced hMSC viability in a dose- and time-dependent manner. Nuclear condensation and fragmentation, chromosomal DNA fragmentation and cytoplasmic vacuolization were observed in Al2O3-NP-exposed cells. The nuclear morphological changes indicated that Al2O3-NPs alter cell cycle progression and gene expression. The cell cycle distribution revealed that Al2O3-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, Al2O3-NPs induced the up-regulation of cell cycle response genes, includingEGR1, E2F1 and CCND1. Our results suggested that exposure to Al2O3-NPs could cause acute cytotoxic effects in hMSCs through cell cycle regulatory genes.