| First Author | Mirkes PE | Year | 2000 |
| Journal | Teratology | Volume | 62 |
| Issue | 1 | Pages | 14-25 |
| PubMed ID | 10861629 | Mgi Jnum | J:63263 |
| Mgi Id | MGI:1860692 | Doi | 10.1002/1096-9926(200007)62:1<14::AID-TERA6>3.0.CO;2-9 |
| Citation | Mirkes PE, et al. (2000) Teratogen-induced activation of ERK, JNK, and p38 MAP kinases in early postimplantation murine embryos. Teratology 62(1):14-25 |
| abstractText | BACKGROUND: Although many teratogens are known to activate apoptotic pathways culminating in abnormal development, little is known about how the embryo transduces a teratogenic exposure into specific responses. Signal reception and transduction are regulated by a number of signal transduction pathways, including the extracellular signal-regulated protein kinases (ERKs), c-Jun N-terminal kinases (JNKs) and the stress-activated protein kinase, p38. METHODS: To analyze the effects of teratogens on MAP kinases, we used whole embryo culture, Western blot analyses, and antibodies recognizing inactive or active MAP kinases, or both. RESULTS: We show that heat shock (HS) induces a rapid, strong, but transient activation of ERK, JNK, and p38 with maximal activation occurring within 30 min of the heat shock. By contrast, cyclophosphamide (CP) and staurosporine (ST) failed to activate ERK or JNK during the time period studied (7. 5 hr). ST and CP did induce a low but reproducible activation of p38 beginning at around 3 hr and 5 hr, respectively, after the initiation of exposure. Previous work has shown that heat shock induces elevated cell death in the embryo, primarily in the developing neuroepithelium, but not in the embryonic heart. Thus, we also compared the activation of these three MAP kinase pathways in heads, hearts, and trunks isolated from day 9 embryos exposed to 43 degrees C for 15 min. The results show that ERK, JNK, and p38 are activated in heads, hearts, and trunks. CONCLUSIONS: Our results show that day 9 embryos do activate MAP kinase signaling pathways in response to teratogenic exposures; however, activation of a particular pathway does not appear to be required for teratogen-induced apoptosis. Copyright 2000 Wiley-Liss, Inc. |
