Expression of Selected Apoptosis Related Genes, MIF, IGIF and TNFα, during Retinoic Acid-Induced Neural Differentiation in Murine Embryonic Stem Cells

Cell Structure and Function

Suparna A. Sarkar¹  Raghubir P. Sharma¹ 

[1] Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia

关键词: apoptosis;    embryonic stem cells;    all-trans-retinoic acid;    differentiation;    MIF;    IL-18;   

DOI  :  10.1247/csf.27.99

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(48)Cited-By(11)Apoptosis plays an important role during embryonic development. Apoptotic cell death is executed by caspases and can be regulated by the Bcl-2 family of genes. Ribonuclease protection assay was used to investigate the expression of selected apoptosis-related genes of the Bcl-2 family, pro-apoptotic Bax, Bad and anti-apoptotic Bcl-2, during differentiation of murine embryonic stem cells (ES) mediated by all-trans-retinoic acid. The mRNA expression of caspase 3, caspase 6 and certain pro-inflammatory cytokines was also investigated simultaneously. ES cells exposed to 1 μM all-trans-retinoic acid on day 8, 9 and 10 of differentiation revealed increased expression of Bax and Bad compared to the vehicle-treated cells. No effect on Bcl-2 mRNA was noted after all-trans-retinoic acid treatment. Increased mRNA expression of caspase 3 and caspase 6 in all-trans-retinoic acid-exposed ES cells suggested that caspases play an important role in retinoic acid-mediated apoptosis during ES differentiation. Increase in the expression of TNFα and macrophage migration inhibitory factor (MIF) was noted in retinoic acid-treated cells on day 14. Significant increase observed in interferon γ inducing factor (IGIF/IL-18) mRNA expression in all-trans-retinoic acid-treated cells on day 14 and 17 did not translate to increased INFγ expression. No change in the expression of other pro-inflammatory cytokines was noted with all-trans-retinoic acid treatment. The function of TNFα, IGIF/IL-18 and MIF in all-trans-retinoic acid-treated cells during ES differentiation and apoptosis is still speculatory. Results suggested that RA-mediated apoptosis during neural differentiation of ES cells involves up-regulation of caspase 3, caspase 6, Bad, and Bax.

【 授权许可】

Unknown