Oishi Katsutaka, Ohkura Naoki, Amagai Noriko, Ishida Norio
Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
FEBS Lett. 2005 Jul 4;579(17):3555-9. doi: 10.1016/j.febslet.2005.05.027.
Diabetes is associated with an excess risk of cardiac events, and one of the risk factors for infarction is the elevated-levels of plasminogen activator inhibitor-1 (PAI-1). To evaluate how the molecular clock mechanism is involved in the diabetes-induced circadian augmentation of PAI-1 gene expression, we examined the expression profiles of PAI-1 mRNA in the hearts of Clock mutant mice with streptozotocin-induced diabetes. Circadian expression of PAI-1 mRNA was blunted to low levels under both normal and diabetic conditions in Clock mutant mice, although the expression rhythm was augmented in diabetic wild-type (WT) mice. Furthermore, plasma PAI-1 levels became significantly higher in WT mice than in Clock mutant mice after STZ administration. Our results suggested that the circadian clock component, CLOCK, is involved in the diabetes-induced circadian augmentation of PAI-1 expression in the mouse heart.
糖尿病与心脏事件的额外风险相关，而梗死的风险因素之一是纤溶酶原激活物抑制剂-1（PAI-1）水平升高。为了评估分子时钟机制如何参与糖尿病诱导的PAI-1基因表达的昼夜节律增强，我们检测了链脲佐菌素诱导的糖尿病Clock突变小鼠心脏中PAI-1 mRNA的表达谱。在正常和糖尿病条件下，Clock突变小鼠中PAI-1 mRNA的昼夜节律表达均减弱至低水平，尽管糖尿病野生型（WT）小鼠的表达节律增强。此外，链脲佐菌素给药后，WT小鼠的血浆PAI-1水平显著高于Clock突变小鼠。我们的结果表明，昼夜节律时钟成分CLOCK参与了糖尿病诱导的小鼠心脏中PAI-1表达的昼夜节律增强。
