| Autor: |
Jiang S; From the Department of Medicine., Park DW; From the Department of Medicine,; the Division of Infectious Diseases, Korea University Ansan Hospital, Ansan 425-707, Republic of Korea., Stigler WS; From the Department of Medicine., Creighton J; Department of Anesthesiology., Ravi S; Department of Pathology, and., Darley-Usmar V; Department of Pathology, and; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0012 and., Zmijewski JW; From the Department of Medicine,; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0012 and. Electronic address: zmijewsk@uab.edu. |
| Abstrakt: |
Defective clearance of apoptotic cells is frequently associated with perpetuation of inflammatory conditions. Our results show a rapid activation of AMP-activated kinase (AMPK) in macrophages upon exposure to apoptotic cells or lysophosphatidylcholine, a specific phospholipid that is produced and released from dying cells. AMPK activation resulted from inhibition of mitochondrial oxygen consumption and ATP production and further depended on Ca(2+) mobilization and mitochondrial reactive oxygen species generation. Once activated, AMPK increased microtubule synthesis and chemokinesis and provided adaptation to energy demand during tracking and engulfment. Uptake of apoptotic cells was increased in lungs of mice that received lysophosphatidylcholine. Furthermore, inhibition of AMPK diminished clearance of apoptotic thymocytes in vitro and in dexamethasone-treated mice. Taken together, we conclude that the mitochondrial AMPK axis is a sensor and enhancer of tracking and removal of apoptotic cell, processes crucial to resolution of inflammatory conditions and a return to tissue homeostasis. |
