atRA-induced apoptosis of mouse embryonic palate mesenchymal cells involves activation of MAPK pathway

Journal Article · Tue Aug 15 04:00:00 EDT 2006 · Toxicology and Applied Pharmacology

OSTI ID:20850393

Zengli, Yu ^[1]; Ying, Xing ^[2]

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1. Department of Nutrition and Food Hygiene, School of Public Health, Zhengzhou University, No. 40 Daxue Road, Zhengzhou 450052 (China)
2. Stem Cell Research Center, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052 (China)

Our previous studies have shown that atRA treatment resulted in cell-cycle block and growth inhibition in mouse embryonic palatal mesenchymal (MEPM). In the current study, gestation day (GD) 13 MEPM cells were used to test the hypothesis that the growth inhibition by atRA is due to apoptosis. The effects of atRA on apoptosis were assessed by performing MTT assay, Cell Death Detection ELISA and flow cytometry, respectively. Data analysis confirmed that atRA treatment induced apoptosis-like cell death, as shown by decreased cell viability and increased fragmented DNA and sub-G1 fraction. atRA-induced apoptosis was associated with upregulation of bcl-2, translocation of bax protein to the mitochondria from the cytosol, activation of caspase-3 and cytochrome c release into cytosol. atRA-induced apoptosis was abrogated by z-DEVD-fmk, a caspase-3 specific inhibitor, and z-VAD-fmk, a general caspase inhibitor, suggesting that the atRA-induced cell death of MEPM cells occurs through the cytochrome c- and caspase-3-dependent pathways. In addition, atRA treatment caused a strong and sustained activation of c-Jun N-terminal kinase (JNK) and p38 kinase (p38), as well as an early but transient activation of extracellular signal-regulated kinase (ERK). Importantly, atRA-induced DNA fragmentation and capase-3 activation were prevented by pretreatment with the JNK inhibitor (SP600125) and the p38 MAPK inhibitor (SB202190), but not by pretreatment with MEK inhibitor (U0126). From these results, we suggest that mitogen-activated protein kinase-dependent pathways is involved in the atRA-induced apoptosis of MEPM cells.

• OSTI ID: 20850393
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 215; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL CYCLE
DATA ANALYSIS
DNA
ENZYME IMMUNOASSAY
GROWTH
INHIBITION
MICE
MITOCHONDRIA
PROTEINS
RETINOIC ACID
TRANSIENTS
TRANSLOCATION