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KMID : 0624620170500100510
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BMB Reports
2017 Volume.50 No. 10 p.510 ~ p.515
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Caspase-2 mediates triglyceride (TG)-induced macrophage cell death
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Lim Jae-Won
Kim Hyun-Kyung
Kim Sung-Hoon
Rhee Ki-Jong
Kim Yoon-Suk
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Abstract
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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 cell death is triggered by caspase-1, and thus investigated the relationship between caspase-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.
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KEYWORD
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Apoptotic caspases, Caspase-1, Caspase-2, THP-1 macrophages, Triglyceride (TG)
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