title: Apoptosis of THP-1 Macrophages Induced by Pseudohypericin-Mediated Sonodynamic Therapy Through the Mitochondria-Caspase Pathway.
abstract: OBJECTIVE
  Pseudohypericin (P-HY) and its congener hypericin are the major hydroxylated phenanthroperylenediones present in Hypericum species. Our previous study indicated that hypericin was able to function as a sonosensitizer. The potential use of P-HY as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. Thus, this study aimed to investigate the effects of P-HY-SDT on THP-1 macrophages.
  
  
  METHODS
  THP-1 macrophages were incubated with P-HY, and cell viability was measured using a CCK-8 assay. Fluorescence microscopy assessed the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm ) and mitochondrial permeability transition pore (mPTP) opening. Apoptotic and necrotic cell levels were measured by the flow cytometry analysis. Western blots were employed to assay BAX, Cytochrome C expression and apoptosis-related proteins.
  
  
  RESULTS
  P-HY-SDT induced THP-1 macrophage apoptosis. The levels of ROS were significantly increased in the SDT group, resulting in both mPTP opening and ΔΨm loss, which led to apoptosis. In addition, the translocation of BAX, release of Cytochrome C and the upregulated expression of apoptosis-related proteins after P-HY-SDT were observed, all of which were reversed by N-acetyl cysteine (NAC).
  
  
  CONCLUSIONS
  P-HY-SDT induced THP-1 macrophage apoptosis through the mitochondria-caspase pathway via ROS generation, the translocation of BAX and the release of Cytochrome C to regulate the mPTP opening.
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, Harbin, PR China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Zheng
authors.forename: Jinrong
authors.initials: J
authors.lastname: Wu
authors.forename: Qun
authors.initials: Q
authors.lastname: Shao
authors.forename: Xuesong
authors.initials: X
authors.lastname: Li
authors.forename: Jiayuan
authors.initials: J
authors.lastname: Kou
authors.forename: Xing
authors.initials: X
authors.lastname: Zhu
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Zhong
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Jiang
authors.forename: Zhongni
authors.initials: Z
authors.lastname: Liu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Liming
authors.initials: L
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D020902:Hypericum / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D014464:Ultrasonic Therapy
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D010569:Perylene; D045304:Cytochromes c; D020169:Caspases; C056602:pseudohypericin