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Major vault protein regulates class A scavenger receptor-mediated tumor necrosis factor-α synthesis and apoptosis in

Jingjing Ben1, Yan Zhang, Rongmei Zhou

  • 1Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China.

The Journal of Biological Chemistry
|May 25, 2013
PubMed

Insights

Major vault protein (MVP) interacts with scavenger receptor A (SR-A) on macrophages, modulating inflammatory responses and apoptosis. This discovery offers new insights into atherosclerosis development and potential therapeutic targets.

Area of Science:

  • Immunology
  • Cell Biology
  • Cardiovascular Research

Background:

  • Atherosclerosis is a chronic inflammatory disease driven by macrophage-derived pro-inflammatory mediators.
  • Scavenger receptor A (SR-A) on macrophages is crucial, but its regulatory mechanisms are unclear.

Purpose of the Study:

  • To identify novel binding partners of SR-A in macrophages.
  • To elucidate the role of SR-A and its interacting proteins in macrophage-mediated inflammation and apoptosis relevant to atherosclerosis.

Main Methods:

  • Immunoprecipitation coupled with mass spectrometry to identify SR-A binding partners.
  • Immunofluorescence staining and chemical cross-linking to confirm protein interactions.
  • Macrophage stimulation with fucoidan (SR-A ligand) and assessment of TNF-α production.
  • Analysis of endocytic pathways (caveolin- vs. clathrin-mediated) and signaling pathways (p38, JNK, ERK).
  • Investigation of MVP localization in lipid rafts and its effect on SR-A-mediated apoptosis.

Main Results:

  • Major vault protein (MVP) was identified as a novel binding partner of SR-A.
  • MVP depletion attenuated fucoidan-induced TNF-α production in macrophages.
  • SR-A-mediated TNF-α synthesis involves caveolin-dependent endocytosis and p38/JNK signaling.
  • MVP enrichment in lipid rafts enhances SR-A, caveolin, and MVP interactions.
  • MVP elimination reduced SR-A-mediated macrophage apoptosis.

Conclusions:

  • MVP fine-tunes SR-A activity in macrophages, influencing pro-inflammatory responses and apoptosis.
  • The SR-A-MVP interaction represents a potential regulatory axis in atherosclerosis pathogenesis.
  • Targeting the SR-A-MVP pathway may offer novel therapeutic strategies for atherosclerosis.
Keywords:
ApoptosisCaveolaeMacrophagesMajor Vault ProteinScavenger ReceptorTumor Necrosis Factor (TNF)

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