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  • Oxidant stress in mitochondrial DNA damage, autophagy and inflammation in atherosclerosis.

Oxidant stress in mitochondrial DNA damage, autophagy and inflammation in atherosclerosis.

Scientific reports (2013-01-18)
Zufeng Ding, Shijie Liu, Xianwei Wang, Magomed Khaidakov, Yao Dai, Jawahar L Mehta
ABSTRACT

Our studies in HUVECs show that ox-LDL induced autophagy and damaged mtDNA leading to TLR9 expression. LOX-1 antibody or the ROS inhibitor apocynin attenuated ox-LDL-mediated autophagy, mtDNA damage and TLR9 expression, suggesting that these events are LOX-1 and ROS-dependent phenomena. Experiments using siRNA to DNase II indicated that DNase II digests mtDNA to protect the tissue from inflammation. Next, we studied and found intense autophagy, TLR9 expression and inflammatory signals (CD45 and CD68) in the aortas of LDLR knockout mice fed high cholesterol diet. Deletion of LOX-1 (LDLR/LOX-1 double knockout mice) attenuated autophagy, TLR9 expression as well as CD45 and CD68. Damaged mtDNA signal was also very high in LDLR knockout mice aortas, and this signal was attenuated by LOX-1 deletion. Thus, it appears that oxidative stress-mediated damaged mtDNA that escapes autophagy induces a potent inflammatory response in atherosclerosis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Deoxyribonuclease II from porcine spleen, Type IV, lyophilized powder, 2,000-6,000 Kunitz units/mg protein (biuret)
Sigma-Aldrich
Deoxyribonuclease II from bovine spleen, Type V, essentially salt-free, lyophilized powder, ≥1,000 units/mg protein