Endogenous oxidoreductase expression is induced by aminoglycosides

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Oxidoreductases, including glutaredoxin (Grx), are crucial enzymes catalyzing thiol-disulfide exchange reactions.
• Glutaredoxin-1 (Grx-1) plays a role in cellular redox homeostasis.
• Aminoglycoside antibiotics are commonly used antimicrobials.

Purpose of the Study:

• To investigate the effect of aminoglycoside antibiotics on Grx-1 expression.
• To explore the underlying mechanisms, particularly the role of oxidative stress.

Main Methods:

• Human cultured retinal pigment epithelial cells were treated with various aminoglycosides (gentamicin, kanamycin, hygromycin) and other compounds.
• Grx-1 expression levels were measured.
• Reactive oxygen species (ROS) formation was assessed.
• Effects of redox modulators (N-acetylcysteine, tert-butyl hydroperoxide) and a transcription factor inducer (phorbol 12-myristate 13-acetate) were examined.

Main Results:

• Aminoglycosides increased Grx-1 expression in a time- and dose-dependent manner.
• Aminoglycoside treatment led to increased reactive oxygen species formation.
• Compounds modulating cellular redox state and AP-1 transcription factor influenced Grx-1 expression consistent with an oxidative stress response.

Conclusions:

• Aminoglycosides induce Grx-1 expression in retinal pigment epithelial cells.
• This induction appears to be a response to aminoglycoside-induced oxidative stress.
• The findings suggest a novel link between aminoglycoside exposure and cellular redox regulation.