HSP70, MAPK, Caspase-3 In The Development Of Neural Tube Defects Caused By Hyperthermia

Objective Neural tube defects (NTD) are the most common congenital malformations caused by varieties of environmental factors, such as hyperthermia, chemical substance, virus infection, smoking and drinking etc. Hyperthermia is a physical teratogenesis which occurs frequently and difficult to be avoided. Recently a retrospective case control study showed that many kinds of human congenital malformations especially NTD could be induced by hyperthermia. Although the underlying mechanisms of NTD caused by hyperthermia are remain unknown. So far some hypotheses have been produced, such as the theory of'heat shock'etc. It is considered that hyperthermia had an effects on the expression of differentiation associate genes during organogenesis of development, and resulted in abnormal biogenesis of differentiation associated proteins, for example some enzyme and transduction proteins, thereby giving rise to the development of malformations. According to this hypothesis, the experiment was worked out to explore the cellular and molecular mechanisms of HSP70,ERK1/2,JNK1/2 and Caspase-3 in the development of NTD caused by hyperthermia.AIM To study the expression and the role of HSP70,ERK1/2,JNK1/2 pathway and Caspase-3 in the development of neural tube defects caused by hyperthermia.METHODS Pregnant golden hamsters in the hyperthermia group were immersed in hot water(42℃) for 20min on GD8. After treatment of 2,8,16,24,48 and 72h, the hamsters were terminated after anesthesia and the embryos were removed form the fetal membrane.The animal models were caused by hyperthermia and the expression of, and divided into the hyperthermia group (2-72h,42℃) and the control group(2-72h,37℃). Expressions of the HSP70, ERK1/2, p-ERK1/2, JNK1/2 p-JNK1/2 and Caspase-3 were measured by Western blotting in the control group and the hyperthermia group.RESULTS HSP70 was steadily expressed in each control group, the expression of HSP70 increased and have a significant difference from that in the corresponding control group at 2-48h(p<0.05);p-ERK1/2 steadily expressed in each control group, and the expression of p-ERK1/2 significantly decreased, which was different from that in the corresponding control group at 8-48h (p<0.05); p-JNK1/2 activity increased in the hyperthermia group and the amount of p-JNK1/2 increased compared with the control group, and the peak appeared in 16h group at 8-48h (p<0.05); Caspase-3 activity increased in the hyperthermia group, the amount of Caspase-3 increased compared with the control group at 8-48h (p<0.05).CONCLUSIONS The expression of HSP70 can be induced to a higher level when exposed to hyperthermia and it may play a role in keeping the embryos survival; Hyperthermia induced a decrease of P-ERK1/2 expression and increased expression of P-JNK1/2 in MAPK pathway, that broke the balance of cell proliferation and apoptosis, and Caspase-3 is stimulated by hyperthermia, which maybe an important way in the development of neural tube defects caused by hyperthermia.KEY WORDS Hyperthermia, induced; Abnormalities; HSP70; Mitogen-Activated Protein Kinases Kinases; Caspases; Golden hamster; Apoptosis...