The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages
Xuesong Li,1,* Lei Gao,2,* Longbin Zheng,1 Jiayuan Kou,1 Xing Zhu,1 Yueqing Jiang,1 Zhaoyu Zhong,1 Juhua Dan,1 Haobo Xu,3 Yang Yang,3 Hong Li,1 Sa Shi,1 Wenwu Cao,4,5 Yajun Zhao,1 Ye Tian,1,3 Liming Yang1 1Department of Pathophysiology, Harbin Medical University, Harbin, People’s Republi...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2015
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/122172aa67db4f239393d7c20b3eda5a |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:122172aa67db4f239393d7c20b3eda5a |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:122172aa67db4f239393d7c20b3eda5a2021-12-02T01:34:06ZThe efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages1178-2013https://doaj.org/article/122172aa67db4f239393d7c20b3eda5a2015-01-01T00:00:00Zhttp://www.dovepress.com/the-efficacy-and-mechanism-of-apoptosis-induction-by-hypericin-mediate-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Xuesong Li,1,* Lei Gao,2,* Longbin Zheng,1 Jiayuan Kou,1 Xing Zhu,1 Yueqing Jiang,1 Zhaoyu Zhong,1 Juhua Dan,1 Haobo Xu,3 Yang Yang,3 Hong Li,1 Sa Shi,1 Wenwu Cao,4,5 Yajun Zhao,1 Ye Tian,1,3 Liming Yang1 1Department of Pathophysiology, Harbin Medical University, Harbin, People’s Republic of China; 2Electron Microscopy Centre, Harbin Medical University, Harbin, People’s Republic of China; 3Division of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, People’s Republic of China; 4Laboratory of Sono- and Photo-theranostic Technologies, Harbin Institute of Technology, Harbin, People’s Republic of China; 5Materials Research Institute, The Pennsylvania State University, University Park, PA, USA *These authors contributed equally to this work Purpose: To investigate the sonoactivity of hypericin (HY), together with its sonodynamic effect on THP-1 macrophages and the underlying mechanism.Materials and methods: CCK-8 was used to examine cell viability. Confocal laser scanning microscopy was performed to assess the localization of HY in cells, reactive oxygen species (ROS) generation, and opening of the mitochondrial permeability transition pore (mPTP) after different treatments. Apoptosis was analyzed using Hoechst–propidium iodide and transmission electron microscopy. Mitochondrial membrane potential (ΔΨm) collapse was detected via fluorescence microscopy. Lipoprotein oxidation was determined in malondialdehyde (MDA) assays. Western blotting was conducted to determine the translocation of BAX and cytochrome C and the expression of apoptosis-related proteins.Results: HY was sublocalized among the nuclei and the mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome in the cytosol of THP-1 macrophages. Under low-intensity ultrasound irradiation, HY significantly decreased cell viability and induced apoptosis. Furthermore, greater ROS generation, higher MDA levels, and greater ΔΨm loss were observed in the sonodynamic therapy (SDT) group. Both ROS generation and MDA levels were significantly reduced by the ROS scavenger N-acetyl cysteine (NAC) and the singlet oxygen scavenger sodium azide. Most of the loss of ΔΨm was inhibited by pretreatment with NAC, sodium azide, and the mPTP inhibitor cyclosporin A (CsA). mPTP opening was induced upon SDT but was reduced by pretreatment with bongkrekic acid, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium, CsA, and NAC. Western blot analyses revealed translocation of BAX and cytochrome C, downregulated expression of Bcl-2, and upregulated expression of cleaved caspase-9, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase in the SDT group, which were reversed by NAC.Conclusion: HY mediated SDT-induced apoptosis in THP-1 macrophages via ROS generation. Then, the proapoptotic factor BAX translocated from the cytosol to the mitochondria, increasing the ratio of BAX/Bcl-2, and the mPTP opened to release cytochrome C. This study demonstrated the great potential of HY-mediated SDT for treating atherosclerosis. Keywords: apoptosis, hypericin, sonodynamic therapy, mitochondria–caspase pathway, atherosclerosisLi XSGao LZheng LBKou JYZhu XJiang YQZhong ZYDan JHXu HBYang YLi HShi SCao WWZhao YJTian YYang LMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 821-838 (2015) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine (General) R5-920 |
| spellingShingle |
Medicine (General) R5-920 Li XS Gao L Zheng LB Kou JY Zhu X Jiang YQ Zhong ZY Dan JH Xu HB Yang Y Li H Shi S Cao WW Zhao YJ Tian Y Yang LM The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages |
| description |
Xuesong Li,1,* Lei Gao,2,* Longbin Zheng,1 Jiayuan Kou,1 Xing Zhu,1 Yueqing Jiang,1 Zhaoyu Zhong,1 Juhua Dan,1 Haobo Xu,3 Yang Yang,3 Hong Li,1 Sa Shi,1 Wenwu Cao,4,5 Yajun Zhao,1 Ye Tian,1,3 Liming Yang1 1Department of Pathophysiology, Harbin Medical University, Harbin, People’s Republic of China; 2Electron Microscopy Centre, Harbin Medical University, Harbin, People’s Republic of China; 3Division of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, People’s Republic of China; 4Laboratory of Sono- and Photo-theranostic Technologies, Harbin Institute of Technology, Harbin, People’s Republic of China; 5Materials Research Institute, The Pennsylvania State University, University Park, PA, USA *These authors contributed equally to this work Purpose: To investigate the sonoactivity of hypericin (HY), together with its sonodynamic effect on THP-1 macrophages and the underlying mechanism.Materials and methods: CCK-8 was used to examine cell viability. Confocal laser scanning microscopy was performed to assess the localization of HY in cells, reactive oxygen species (ROS) generation, and opening of the mitochondrial permeability transition pore (mPTP) after different treatments. Apoptosis was analyzed using Hoechst–propidium iodide and transmission electron microscopy. Mitochondrial membrane potential (ΔΨm) collapse was detected via fluorescence microscopy. Lipoprotein oxidation was determined in malondialdehyde (MDA) assays. Western blotting was conducted to determine the translocation of BAX and cytochrome C and the expression of apoptosis-related proteins.Results: HY was sublocalized among the nuclei and the mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome in the cytosol of THP-1 macrophages. Under low-intensity ultrasound irradiation, HY significantly decreased cell viability and induced apoptosis. Furthermore, greater ROS generation, higher MDA levels, and greater ΔΨm loss were observed in the sonodynamic therapy (SDT) group. Both ROS generation and MDA levels were significantly reduced by the ROS scavenger N-acetyl cysteine (NAC) and the singlet oxygen scavenger sodium azide. Most of the loss of ΔΨm was inhibited by pretreatment with NAC, sodium azide, and the mPTP inhibitor cyclosporin A (CsA). mPTP opening was induced upon SDT but was reduced by pretreatment with bongkrekic acid, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium, CsA, and NAC. Western blot analyses revealed translocation of BAX and cytochrome C, downregulated expression of Bcl-2, and upregulated expression of cleaved caspase-9, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase in the SDT group, which were reversed by NAC.Conclusion: HY mediated SDT-induced apoptosis in THP-1 macrophages via ROS generation. Then, the proapoptotic factor BAX translocated from the cytosol to the mitochondria, increasing the ratio of BAX/Bcl-2, and the mPTP opened to release cytochrome C. This study demonstrated the great potential of HY-mediated SDT for treating atherosclerosis. Keywords: apoptosis, hypericin, sonodynamic therapy, mitochondria–caspase pathway, atherosclerosis |
| format |
article |
| author |
Li XS Gao L Zheng LB Kou JY Zhu X Jiang YQ Zhong ZY Dan JH Xu HB Yang Y Li H Shi S Cao WW Zhao YJ Tian Y Yang LM |
| author_facet |
Li XS Gao L Zheng LB Kou JY Zhu X Jiang YQ Zhong ZY Dan JH Xu HB Yang Y Li H Shi S Cao WW Zhao YJ Tian Y Yang LM |
| author_sort |
Li XS |
| title |
The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages |
| title_short |
The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages |
| title_full |
The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages |
| title_fullStr |
The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages |
| title_full_unstemmed |
The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages |
| title_sort |
efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in thp-1 macrophages |
| publisher |
Dove Medical Press |
| publishDate |
2015 |
| url |
https://doaj.org/article/122172aa67db4f239393d7c20b3eda5a |
| work_keys_str_mv |
AT lixs theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT gaol theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT zhenglb theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT koujy theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT zhux theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT jiangyq theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT zhongzy theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT danjh theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT xuhb theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT yangy theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT lih theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT shis theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT caoww theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT zhaoyj theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT tiany theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT yanglm theefficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT lixs efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT gaol efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT zhenglb efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT koujy efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT zhux efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT jiangyq efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT zhongzy efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT danjh efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT xuhb efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT yangy efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT lih efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT shis efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT caoww efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT zhaoyj efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT tiany efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages AT yanglm efficacyandmechanismofapoptosisinductionbyhypericinmediatedsonodynamictherapyinthp1macrophages |
| _version_ |
1718402999850631168 |