Paclitaxel-induced peripheral neuropathy is caused by epidermal ROS and mitochondrial damage through conserved MMP-13 activation.

Scientific Reports
Anthony M CirrincioneSandra Rieger

Abstract

Paclitaxel induces peripheral neuropathy as a side effect of cancer treatment. The underlying causes are unclear, but epidermal, unmyelinated axons have been shown to be the first to degenerate. We previously utilized an in vivo zebrafish model to show that the epidermal matrix-metalloproteinase 13 (MMP-13) induces degeneration of unmyelinated axons, whereas pharmacological inhibition of MMP-13 prevented axon degeneration. However, the precise functions by which MMP-13 is regulated and affects axons remained elusive. In this study, we assessed mitochondrial damage and reactive oxygen species (ROS) formation as possible inducers of MMP-13, and we analyzed MMP-13-dependent damage. We show that the small ROS, H2O2, is increased in basal keratinocytes following treatment with paclitaxel. Cytoplasmic H2O2 appears to derive, at least in part, from mitochondrial damage, leading to upregulation of MMP-13, which in turn underlies increased epidermal extracellular matrix degradation. Intriguingly, also axonal mitochondria show signs of damage, such as fusion/fission defects and vacuolation, but axons do not show increased levels of H2O2. Since MMP-13 inhibition prevents axon degeneration but does not prevent mitochondrial vacuolation, we...Continue Reading

References

Jan 31, 1978·Psychopharmacology·R L Collins, G Whitney
Jul 1, 1994·Journal of Neuroscience Methods·S R ChaplanT L Yaksh
Oct 1, 1997·Journal of Neuro-oncology·P A ForsythL M DeAngelis
Aug 11, 2001·Free Radical Biology & Medicine·G VarbiroB Sumegi
May 25, 1958·The Journal of Biophysical and Biochemical Cytology·J D LEVER, J B CHAPPELL
Jul 24, 2004·The International Journal of Developmental Biology·Dominique Le GuellecJean-Yves Sire
Mar 24, 2006·Nature Methods·Vsevolod V BelousovSergey Lukyanov
Jul 11, 2009·The American Journal of Pathology·Noriko HattoriYasunori Okada
Mar 15, 2011·The European Journal of Neuroscience·Gary J BennettChiang Siau
Jul 6, 2014·Physiological Reviews·Dmitry B ZorovSteven J Sollott
Mar 6, 2015·Journal of Visualized Experiments : JoVE·Thomas S LisseSandra Rieger
Apr 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Thomas S LisseSandra Rieger
Apr 27, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jijun XuFeng Lin

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Citations

Jun 19, 2021·The Ocular Surface·Jeremy Chung Bo ChiangMaria Markoulli
Jul 23, 2021·Expert Opinion on Therapeutic Targets·Ramandeep SinghShyam Sunder Sharma
Aug 27, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Tiffany LiSusanna B Park

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Methods Mentioned

BETA
amputation
transmission electron microscopy
transgenic
PCR
fluorescence microscopy

Software Mentioned

Imaris
Adobe Illustrator
MetaMorph Outgrowth
GraphPad
Prism7
Prism GraphPad
ZEN
HyPer
Photoshop

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