Potential involvement of the 18 kDa translocator protein and reactive oxygen species in apoptosis of THP-1 macrophages induced by sonodynamic therapy

PLoS One. 2018 May 10;13(5):e0196541. doi: 10.1371/journal.pone.0196541. eCollection 2018.

Abstract

Sonodynamic therapy (SDT) with exogenous protoporphyrin IX (PpIX) or endogenous PpIX derived from 5-aminolevulinic acid (ALA) has been carried out to produce apoptotic effects on macrophages, indicating a potential treatment methodology for atherosclerosis. Our previous studies have found that mitochondria damage by reactive oxygen species (ROS) plays a major role in the SDT-induced apoptosis. This study aimed at investigating the potential involvement of the mitochondrial 18 kDa translocator protein (TSPO) and ROS in the pro-apoptotic effects of SDT on THP-1 macrophages. THP-1 macrophages were divided into control and SDT groups, and went through pretreatment of the specific TSPO ligand PK11195 and ROS scavengers N-Acetyl Cysteine (NAC), then compared with groups without pretreatment. Application of PK11195 reduced intracellular accumulation of endogenous PpIX. PK11195 and NAC reduced the generation of intracellular ROS and oxidation of cardiolipin induced by SDT, respectively. PK11195 and NAC also reduced SDT-induced mitochondrial membrane potential (ΔΨm) loss, the translocation of cytochrome c and cell apoptosis. PpIX accumulation, ROS generation and cell apoptosis were also attenuated by siTSPO. Our findings indicate the pivotal role of TSPO and ROS in SDT-induced cardiolipin oxidation, ΔΨm collapse, cytochrome c translocation and apoptosis in THP-1 macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Humans
  • Macrophages / metabolism
  • Macrophages / physiology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / metabolism
  • Protoporphyrins
  • Reactive Oxygen Species / metabolism
  • Receptors, GABA / metabolism*
  • Receptors, GABA / physiology
  • THP-1 Cells / physiology
  • Ultrasonic Therapy / methods*

Substances

  • Protoporphyrins
  • Reactive Oxygen Species
  • Receptors, GABA
  • TSPO protein, human
  • Aminolevulinic Acid
  • Cytochromes c
  • protoporphyrin IX

Grants and funding

This study was supported by the National Natural Science Foundation of China (NSFC) (81400339 and 81701848), the State Key Program of NSFC (81530052), Natural Science Foundation of Heilongjiang Province (QC2016121), and Medical Scientific Research Foundation of Harbin Medical University (2016LCZX57). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.