Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 136, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2021.106003
Keywords
CD137; Macrophage; Apoptosis; Mitochondrial dynamics; Atherosclerosis
Categories
Funding
- National Natural Science Foundation of China [81970379, 81670405]
Ask authors/readers for more resources
CD137 signaling induces macrophage apoptosis by promoting mitochondrial fission dependent on the p38 MAPK pathway.
Background: CD137 signaling is an essential factor in cell fate and atherosclerosis. An increase in the number of apoptotic macrophages accelerates atherosclerotic development involving mitochondrial dynamics.However, the role of CD137 signaling in macrophage apoptosis and changes in mitochondria has not been demonstrated clearly. Methods and Results: Here, we used ApoE-/- mice as a model of atherosclerotic plaques. Mouse agonist antiCD137 L and inhibitory anti-CD137 antibody were used to activate or block the CD137 signaling, respectively. Treatment of ApoE-/- mice with agonist anti-CD137 L promoted the formation of necrotic cores and macrophage apoptosis in plaques. Further, activation of CD137 signaling caused macrophage apoptosis in vitro, with upregulation of caspase-9 and caspase-3 expression and an increase in the Bax/Bcl-2 ratio. Meanwhile, CD137 signaling promoted mitochondrial fission observed by mitochondrial fragmentation. Interestingly, inhibition of mitochondrial dynamin-related protein 1 (Drp1) using Mdivi-1 reduced the expression of pro-apoptotic proteins and the amounts of apoptotic macrophages induced by CD137 signaling. Finally, we also found that the p38 MAPK pathway activated by CD137 signaling increased the expression of Drp1 expression and number of mitochondrial fragmented structures. Inhibition of the p38 MAPK pathway by SB203580 attenuated mitochondrial dysfunction through reducing mitochondrial membrane potential loss, cytochrome c release, and mitochondrial reactive oxygen species (ROS) generation. Conclusions: Overall, we identify a novel mechanism whereby CD137 signaling induces macrophage apoptosis through promoting mitochondrial fission dependent on the p38 MAPK pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available