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. 2024 Sep 27;19(9):e0306498.
doi: 10.1371/journal.pone.0306498. eCollection 2024.

Proteomic analysis of dorsal root ganglia in a mouse model of paclitaxel-induced neuropathic pain

Rania Hanna  1 , Alexandru Graur  2 , Patricia Sinclair  1 , Bryan D Mckiver  3 , Paula D Bos  4 , M Imad Damaj  3 , Nadine Kabbani  1   2
Affiliations

Proteomic analysis of dorsal root ganglia in a mouse model of paclitaxel-induced neuropathic pain

Rania Hanna et al. PLoS One. .

Abstract

Paclitaxel is a chemotherapy drug widely used for the treatment of various cancers based on its ability to potently stabilize cellular microtubules and block division in cancer cells. Paclitaxel-based treatment, however, accumulates in peripheral system sensory neurons and leads to a high incidence rate (over 50%) of chemotherapy induced peripheral neuropathy in patients. Using an established preclinical model of paclitaxel-induced peripheral neuropathy (PIPN), we examined proteomic changes in dorsal root ganglia (DRG) of adult male mice that were treated with paclitaxel (8 mg/kg, at 4 injections every other day) relative to vehicle-treated mice. High throughput proteomics based on liquid chromatography electrospray ionization mass spectrometry identified 165 significantly altered proteins in lumbar DRG. Gene ontology enrichment and bioinformatic analysis revealed an effect of paclitaxel on pathways for mitochondrial regulation, axonal function, and inflammatory purinergic signaling as well as microtubule activity. These findings provide insight into molecular mechanisms that can contribute to PIPN in patients.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. A workflow schematic showing the study design.
Fig 2
Fig 2. Effect of paclitaxel on the DRG proteome.
Volcano plot distribution of significantly altered proteins within the DRG. A) Cytosolic fraction. B) Membrane fraction. GO terms associated with significantly altered proteins in paclitaxel treated mice relative to controls. Cytosolic protein fraction cellular component (C), molecular function (D), biological process. (E). Membrane protein fraction cellular component (F), molecular function (G), biological process (H).
Fig 3
Fig 3. A protein-protein interaction (PPI) map of the paclitaxel associated DRG proteome.
STRING network showing PPI amongst all significantly altered proteins. Protein clusters within the network are highlighted by color. The thickness of the connection indicates the degree of confidence between node associations while color indicates whether the protein is increased (red), decreased (green) or differentially altered (light brown) by paclitaxel. The STRING network is based on an MCL algorithm with an inflation parameter of 2 used to identify 11 cluster groups.
Fig 4
Fig 4. Primary cluster groups within the PPI network.
An enrichment tag analysis showing the 11 cluster groups within the STRING analysis of the paclitaxel associated DRG proteome.
Fig 5
Fig 5. A signaling pathway hypothesis model showing the effect of paclitaxel on proteins within the DRG.
See this image and copyright information in PMC

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References

    1. Belani CP. Paclitaxel and docetaxel combinations in non-small cell lung cancer. Chest. 2000;117: 144S–151S. doi: 10.1378/chest.117.4_suppl_1.144s - DOI - PubMed
    1. Nathan FE, Berd D, Sato T, Mastrangelo MJ. Paclitaxel and tamoxifen: An active regimen for patients with metastatic melanoma. Cancer. 2000;88: 79–87. doi: 10.1002/(sici)1097-0142(20000101)88:1<79::aid-cncr12>3.0.co;2-l - DOI - PubMed
    1. Polomano RC, Farrar JT. Pain and neuropathy in cancer survivors. Surgery, radiation, and chemotherapy can cause pain; research could improve its detection and treatment. Am J Nurs. 2006;106: 39–47. doi: 10.1097/00000446-200603003-00015 - DOI - PubMed
    1. Kawashiri T, Inoue M, Mori K, Kobayashi D, Mine K, Ushio S, et al.. Preclinical and Clinical Evidence of Therapeutic Agents for Paclitaxel-Induced Peripheral Neuropathy. Int J Mol Sci. 2021;22: 8733. doi: 10.3390/ijms22168733 - DOI - PMC - PubMed
    1. Risinger AL, Riffle SM, Lopus M, Jordan MA, Wilson L, Mooberry SL. The taccalonolides and paclitaxel cause distinct effects on microtubule dynamics and aster formation. Mol Cancer. 2014;13: 41. doi: 10.1186/1476-4598-13-41 - DOI - PMC - PubMed

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