5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Inhibits RIPK1/RIPK3-Dependent Necroptosis in THP-1-Derived Foam Cells

Fang Tian, Jianting Yao, Meng Yan, Xin Sun, Wei Wang, Weiwei Gao, Zhen Tian, Shuyuan Guo, Zengxiang Dong, Bicheng Li, Tielei Gao, Peng Shan, Bing Liu, Haiyang Wang, Jiali Cheng, Qianping Gao, Zhiguo Zhang, Wenwu Cao, Ye Tian

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Abstract

Necroptosis, or programmed necrosis, contributes to the formation of necrotic cores in atherosclerotic plaque in animal models. However, whether inhibition of necroptosis ameliorates atherosclerosis is largely unknown. In this study, we demonstrated that necroptosis occurred in clinical atherosclerotic samples, suggesting that it may also play an important role in human atherosclerosis. We established an in vitro necroptotic model in which necroptosis was induced in THP-1-derived foam cells by serum deprivation. With this model, we demonstrated that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) inhibited necroptosis while promoting apoptosis. ALA-SDT activated the caspase-3 and caspase-8 pathways in foam cells, which is responsible for the switch from necroptosis to apoptosis. The inhibition of either caspase-8 or caspase-3 abolished the anti-necroptotic effect of ALA-SDT. In addition, we found that caspase-3 activation peaked 4 hours after ALA-SDT treatment, 2 hours earlier than maximal caspase-8activation. Taken together, our data indicate that ALA-SDT mediates the switch from necroptosis to apoptosis by activating the caspase-3 and caspase-8 pathways and may improve the prognosis of atherosclerosis.

Original languageEnglish (US)
Article number21992
JournalScientific reports
Volume6
DOIs
StatePublished - Feb 25 2016

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Tian, F., Yao, J., Yan, M., Sun, X., Wang, W., Gao, W., Tian, Z., Guo, S., Dong, Z., Li, B., Gao, T., Shan, P., Liu, B., Wang, H., Cheng, J., Gao, Q., Zhang, Z., Cao, W., & Tian, Y. (2016). 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Inhibits RIPK1/RIPK3-Dependent Necroptosis in THP-1-Derived Foam Cells. Scientific reports, 6, [21992]. https://doi.org/10.1038/srep21992