Study summary · research use only
Mechano growth factor interacts with nucleolin to protect against cisplatin-induced neurotoxicity
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study (species not specified), researchers examined whether mechano growth factor (MGF) protects dorsal root ganglion (DRG) neurons from cisplatin-induced neurotoxicity. Endogenous MGF expression in DRG neurons was reported to reduce cisplatin-induced thermal hyperalgesia, and exogenous MGF and a modified form with an added N-terminal cysteine (CMGF) protected embryonic DRG neurons from cisplatin-induced cell death in culture. Mass spectroscopy identified nucleolin as a key MGF-binding partner, and antibodies against nucleolin blocked the protective effect of MGF and CMGF in culture. Nucleolin and MGF were both located in the DRG neuron nucleolus, and RNA sequencing suggested MGF may be involved in RNA processing, protein targeting, and transcription/translation, which the authors link to nucleolin's role in cisplatin-induced neurotoxicity.
Abstract
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.
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