Common increase of GATA-3 level in PC-12 cells by three teratogens causing autism spectrum disorders.
Autism spectrum disorder (ASD) is a disease of neuro-developmental origin of uncertain etiology. The current understanding is that both genetic and environmental factors contribute to the development of ASD. Exposure to valproate, thalidomide and alcohol during gestation are amongst the environmental triggers that are associated with the development of ASD. These teratogens may disturb the ontogeny of the brain by altering the expression pattern of genes that regulate the normal development of the brain. In this study, a neuron-like PC-12 cell model was used to examine the effects of these compounds on the binding potential of 50 different transcription factors to understand the molecular mechanism/s that may be involved in the teratogenesis caused by these agents. Cells in culture were treated with low or high concentrations of teratogens within a range that are reported in the blood of individuals. A pronounced increase in GATA transcription factor binding was observed for all three teratogens. Furthermore, Western blot analysis showed that GATA-3 level in the nuclear fractions was enhanced by each of the three teratogens. Results suggest that altered gene expression pattern due to heightened GATA-3 activities in the fetral brains following exposure to these teratogens may contribute to the development of ASD.
Division of Pediatric Surgery, Department of Surgery, and the Departments of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. urout@surgery.umsmed.edu
Ujjwal K
UK
Rout
Pete
P
Clausen
D000818:Animals; D001321:Autistic Disorder / Q000139:chemically induced*; D000431:Ethanol / Q000633:toxicity*; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D020869:Gene Expression Profiling; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D013723:Teratogens / Q000633:toxicity*; D013792:Thalidomide / Q000633:toxicity*; D014157:Transcription Factors / Q000378:metabolism; D014635:Valproic Acid / Q000633:toxicity*
D050990:GATA3 Transcription Factor; D013723:Teratogens; D014157:Transcription Factors; D000431:Ethanol; D013792:Thalidomide; D014635:Valproic Acid