Macrophage migration ihibitory factor stimulates AMP-activated protein kinase in the ischaemic heart (Nature, 2008, 451:578-582)

報告日期: 2008/06/03
報告時間: 17:10/18:00
報告學生: 鍾憲輝(英文報告)
講評老師: 簡基憲
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/970603-3.pdf

Macrophage migration inhibitory factor stimulates       AMP-activated protein kinase in the ischaemic heart

Edward J. Miller , Ji Li , Courtney McDonald , Toshiya Atsumi , Richard Bucala & Lawrence H. Young

Nature 451: 578-582, 2008

 

Speaker: Chung, Hsien-Hui                              

Commentator: Chien, Chi-Hsien                           

Date: 2008/6/3

Place: Room 602

 

Macrophage migration inhibitory factor (MIF) is an upstream activator of monocytes/macrophages, and it is centrally involved in the pathogenesis of septic shock, arthritis, and other inflammatory conditions. Then, MIF is expressed in several cell types, including monocytes/macrophages, vascular smooth muscle and cardiomyocytes. Previous studies indicated that circulating hormones can activate AMP-activated protein kinase (AMPK), and the activation of AMPK mediates ischaemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. But the possible mechanism of MIF in regulating AMPK has not been clarified. In this article, the authors showed that MIF can stimulate AMPK activation through CD74 in the ischaemic heart, which promotes glucose uptake and protects the heart from ischaemia-reperfusion injury. In addition, they generated Mif-/- mice to investigate the abrogation of MIF in ischaemic AMPK signaling, which impaired ischaemic heart AMPK activation, glucose uptake, and post-ischaemic cardiac function. Moreover, they also found that human fibroblasts with a low-activity MIF promoter polymorphism (5-CATT allele) decreased MIF release and AMPK pathway during ischaemia. Therefore, MIF not only modulates the activation of cardioprotective AMPK pathway during ischaemia, but also provides a potential target for improving coronary artery disease, and a common polymorphism in human MIF promoter may influence AMPK activation.  

 

References:

1. Leng, L. et al. MIF signal transduction initiated by binding to CD74. J. Exp. Med. 197: 1467-1476, 2003

2. Benigni, F. et al. The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle. J. Clin. Invest. 106: 1291-1300, 2000