Involvement of circadian clock gene Clock in diabetes-induced circadian augmentation of plasminogen activator inhibitor-1 (PAI-1) expression in the mouse heart.
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.
Oishi
Katsutaka
K
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.
Ohkura
Naoki
N
Amagai
Noriko
N
Ishida
Norio
N
D000818:Animals; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D015534:Trans-Activators; D056926:CLOCK Proteins; C538944:Clock protein, mouse