Mechano growth factor interacts with nucleolin to protect against cisplatin-induced neurotoxicity.

Autor: Podratz JL; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America., Tang JJ; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America., Polzin MJ; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America., Schmeichel AM; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America., Nesbitt JJ; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America., Windebank AJ; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America. Electronic address: windebank.anthony@mayo.edu., Madigan NN; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2020 Sep; Vol. 331, pp. 113376. Date of Electronic Publication: 2020 Jun 05.
DOI: 10.1016/j.expneurol.2020.113376
Abstrakt: Mechano growth factor (MGF) is an alternatively spliced form of insulin-like growth factor-1 (IGF-1) that has shown to be neuroprotective against 6-hydroxydopamine toxicity and ischemic injury in the brain. MGF also induces neural stem cell proliferation in the hippocampus and preserves olfactory function in aging mice. Cisplatin is a chemotherapy drug that induces peripheral neuropathy in 30-40% of treated patients. Our studies were designed to see if MGF would protect dorsal root ganglion (DRG) neurons from cisplatin-induced neurotoxicity and to identify potential mechanisms that may be involved. Expression of endogenous MGF in adult DRG neurons in vivo ameliorated cisplatin-induced thermal hyperalgesia. Exogenous MGF and MGF with a cysteine added to the N-terminus (CMGF) also protected embryonic DRG neurons from cisplatin-induced cell death in vitro. Mass spectroscopy analysis of proteins bound to MGF showed that nucleolin is a key-binding partner. Antibodies against nucleolin prevented the neuroprotective effect of MGF and CMGF in culture. Both nucleolin and MGF are located in the nucleolus of DRG neurons. RNAseq of RNA associated with MGF indicated that MGF may be involved in RNA processing, protein targeting and transcription/translation. Nucleolin is an RNA binding protein that is readily shuttled between the nucleus, cytoplasm and plasma membrane. Nucleolin and MGF may work together to prevent cisplatin-induced neurotoxicity. Exploring the known mechanisms of nucleolin may help us better understand the mechanisms of cisplatin toxicity and how MGF protects DRG neurons.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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