Oxidative stress-dependent MMP-13 activity underlies glucose neurotoxicity.
Authors Waldron AL, Schroder PA, Bourgon KL, Bolduc JK, Miller JL, Pellegrini AD, Dubois
AL, Blaszkiewicz M, Townsend KL, Rieger S
Submitted By Sandra Rieger on 1/16/2018
Status Published
Journal Journal of diabetes and its complications
Year 2017
Date Published 12/1/2017
Volume : Pages Not Specified : Not Specified
PubMed Reference 29306589
Abstract A complication of diabetes is neuropathy, a condition of sensory axon
degeneration that originates in the epidermis. The mechanisms remain unknown but
reactive oxygen species (ROS) have been implicated in this condition. In this
study, we assessed the role of ROS and a candidate downstream target, MMP-13 in
glucose-induced sensory axon degeneration in zebrafish and mice., The effects of
glucose on metabolism and sensory axon degeneration were assessed using qPCR and
live imaging. ROS were analyzed using pentafluorobenzene-sulfonyl fluorescein
and activation of the NF-?B stress response was determined using Tg(NF-?B:GFP)
zebrafish. The role of MMP-13 and ROS in glucose-dependent axon degeneration was
determined in zebrafish following treatment with the antioxidant,
N-acetylcysteine and the MMP-13 inhibitor, DB04760. Neuropathic mice fed on a
high-fat/high-sugar diet were treated with the MMP-13 inhibitor, CL-82198 to
assess sensory recovery., Glucose treatment of zebrafish induced metabolic
changes that resemble diabetes. Sensory axon degeneration was mediated by
ROS-induced MMP-13 and prevented upon antioxidant treatment or MMP-13
inhibition. MMP-13 inhibition also reversed neuropathy in diabetic mice., We
demonstrate that zebrafish are suitable to study glucose-induced neurotoxicity.
Given the effects in zebrafish and mice, MMP-13 inhibition may be beneficial in
the treatment of human diabetic neuropathy.