Tilorone acts as a lysosomotropic agent in fibroblasts

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Tilorone is an amphiphilic cationic compound known for its antiviral properties.
• Lysosomes are crucial cellular organelles involved in degradation and recycling.

Purpose of the Study:

• To investigate the effects of Tilorone on the lysosomal system.
• To elucidate the mechanism by which Tilorone perturbs lysosomal function.

Main Methods:

• Experiments were conducted using cultured fibroblasts and isolated lysosomes.
• Measurements included sulfated glycosaminoglycan storage, lysosomal enzyme secretion and maturation, and receptor-mediated endocytosis.
• Lysosomal pH and ATP-dependent acidification were assessed.

Main Results:

• Tilorone induced storage of sulfated glycosaminoglycans in fibroblasts.
• It enhanced secretion of precursor lysosomal enzymes and inhibited their maturation.
• Tilorone inhibited receptor-mediated endocytosis and increased lysosomal pH, abolishing ATP-dependent acidification.

Conclusions:

• Tilorone acts as a weak base, accumulating in acidic cellular compartments.
• It raises lysosomal pH, interfering with lysosomal catabolic activity.
• Tilorone disrupts receptor-mediated transport of lysosomal enzymes, affecting cellular processes.