Blocking exosomal secretion aggravated 1,4-benzoquinone-induced cytotoxicity

Area of Science:

• Toxicology
• Cell Biology
• Biochemistry

Background:

• Benzene exposure causes hematotoxicity and leukemia.
• The exact mechanisms of benzene's toxicity are not fully understood.
• Exosomes are emerging as key players in cellular toxicity mechanisms.

Purpose of the Study:

• To investigate the impact of 1,4-benzoquinone (PBQ), a benzene metabolite, on exosome release.
• To determine the role of exosomal secretion in mitigating PBQ-induced cytotoxicity.

Main Methods:

• Isolated and purified exosomes from PBQ-treated HL-60 cells using ultracentrifugation.
• Verified exosome characteristics via transmission electron microscopy, nanoparticle tracking analysis, and biomarker detection.
• Assessed the effect of GW4869, an exosome release inhibitor, on PBQ cytotoxicity.

Main Results:

• PBQ treatment dose-dependently increased exosome secretion in HL-60 cells, peaking at 3 hours with 10 μM PBQ.
• Exosomes derived from PBQ-treated cells were enriched with specific microRNAs (miRNAs), including mir-34a-3p and mir-34A-5p.
• Inhibiting exosome release with GW4869 worsened PBQ-induced cytotoxicity, evidenced by increased reactive oxygen species, decreased mitochondrial potential, and elevated apoptosis.

Conclusions:

• Exosome secretion plays a protective role against 1,4-benzoquinone-induced cytotoxicity.
• Exosomes contribute to maintaining cellular homeostasis during benzene metabolite exposure.
• Understanding exosome function offers potential therapeutic targets for benzene-related hematotoxicity.