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Caspase-2 mediates triglyceride (TG)-induced macrophage cell death
Jaewon Lim1, Sung Hoon Kim1, Hyun-Kyung Kim1,2, Ki-Jong Rhee1, Yoon Suk Kim1,*
1Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, 26493, Republic of Korea,
2Department of Biomedical Laboratory Science, College of Natural Science, Gimcheon University, Gimcheon, 39528, Republic of Korea
Triglyceride (TG) accumulation causes macrophage cell death, which affects the development of atherosclerosis. Here, we examined whether caspase-2 is implicated in TG-induced macrophage cell death. We found that caspase-2 activity is increased in TG-treated THP-1 macrophages, and that inhibition of caspase-2 activity drastically inhibits TG-induced cell death. We previously reported that TG-induced macrophage death is triggered by caspase-1, and thus investigated the relationship between casapse-2 and caspase-1 in TG-induced macrophage cell death. Inhibition of caspase-2 activity decreased caspase-1 activity in TG-treated macrophages. However, caspase-1 inhibition did not affect caspase-2 activity, suggesting that caspase-2 is upstream of caspase-1. Furthermore, we found that TG induces activation of caspase-3, -7, -8, and -9, as well as cleavage of PARP. Inhibition of caspase-2 and -1 decreased TG-induced caspase-3, -7, -8, and -9 activation and PARP cleavage. Taken together, these results suggest that TG-induced macrophage cell death is mediated via the caspase-2/caspase-1/apoptotic caspases/PARP pathways.
Abstract, Accepted Manuscript(in press) [Submitted on June 22, 2017, Accepted on August 1, 2017]
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