Format

Send to

Choose Destination
PLoS One. 2017 Mar 14;12(3):e0173031. doi: 10.1371/journal.pone.0173031. eCollection 2017.

Retinoic acid exacerbates chlorpyrifos action in ensuing adipogenic differentiation of C3H10T½ cells in a GSK3β dependent pathway.

Author information

1
Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India.
2
Centre for Stem Cell Tissue Engineering and Biomedical Excellence, Panjab University, Chandigarh, India.
3
Biotechnology Branch, University Institute of Engineering and Technology, Panjab University, Chandigarh, India.

Abstract

The cell differentiation can be exploited as a paradigm to evaluate the effects of noxious chemicals, on human health, either alone or in combinations. In this regard, the effect of a known cell differentiation agent, retinoic acid (RA) was analyzed in the presence of a noxious chemical chlorpyrifos (CPF), an organophosphate (OP), the receptors of which have recently been localized to mesenchymal stem cells (MSCs). The observed imbalance of adipogenic to skeletal differentiation by CPF together with conundrum about adipogenic potential of RA prompted us to delineate their combinatorial effects on C3H10T½MSC-like undifferentiated cells. Based on MTT assay, the cellular viability was retained by CPF at concentrations ranging from 0.01-50μM, beyond which it caused cytotoxicity. These non-toxic concentrations also mildly interfered with adipogenesis of C3H10T½ cells following exposure to adipogenic cocktail. However, upon exposure to RA alone, these MSCs adopted elongated morphology and accumulated lipid vesicles, by day 20, as discerned by phase-contrast and transmission electron microscopy (TEM), in concert with enhanced Oil Red O stained cells. This effect got strongly augmented upon exposure to combination of CPF and RA in a dose-dependent manner. Simultaneous up-regulation in perilipin-1 (PLIN1) and adipsin (ADN) genes, additionally reiterated the adipogenic differentiation. Mechanistically, GSK3β pathway was found to be a major player, whereby inhibiting it with lithium chloride (LiCl) resulted in complete blockage of lipid accumulation, accompanied by complete down regulation of PLIN1 and ADN gene expression. In conclusion, these observations for the first time, lend evidence that exposure of CPF accompanied by RA directs commitment of C3H10T½ cells to adipogenic differentiation through a process involving a crosstalk at GSK3β signaling.

PMID:
28291828
PMCID:
PMC5349446
DOI:
10.1371/journal.pone.0173031
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center