ArticleProceedings of the National Academy of Sciences of the United States of America2007
Chronic exposure to paclitaxel diminishes phosphoinositide signaling by calpain-mediated neuronal calcium sensor-1 degradation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 107 citations in OpenAlex.
- Blockade of IL-6 signaling prevents paclitaxel-induced neuropathy in C57Bl/6 mice.Cell death & disease · 2020Trial
- Proteomic Adaptations in the Spinal Cord of a Breast Cancer Model of Paclitaxel-Induced Peripheral Neuropathy.Journal of proteome research · 2026Article
- Time‑resolved multi-omic analysis of paclitaxel exposure in human iPSC‑derived sensory neurons unveils mechanisms of chemotherapy‑induced peripheral neuropathy.Cell death & disease · 2026Article
- Paclitaxel-induced adverse effects: insights into multi-organ toxicities and molecular mechanisms.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Monomethyl auristatin E and paclitaxel use different mechanisms to alter intracellular calcium signaling.Biochemical pharmacology · 2025Article
- Results of the preclinical multicenter randomized controlled paclitaxel-induced neuropathy prevention replication study (PINPRICS).BMC research notes · 2025Article
- Dysregulation of calcium homeostasis in cancer and its role in chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Lithium: A Promising Anticancer Agent.Life (Basel, Switzerland) · 2023Review
- Chemobrain in Breast Cancer: Mechanisms, Clinical Manifestations, and Potential Interventions.Drug safety · 2022Review
- Sarm1 activation produces cADPR to increase intra-axonal Ca++ and promote axon degeneration in PIPN.The Journal of cell biology · 2022Article
- A preliminary, prospective study of peripheral neuropathy and cognitive function in patients with breast cancer during taxane therapy.PloS one · 2022Article
- Induced pluripotent stem cell-derived brain organoids as potential human model system for chemotherapy induced CNS toxicity.Frontiers in molecular biosciences · 2022Article
- Aberrant calcium signalling downstream of mutations in TP53 and the PI3K/AKT pathway genes promotes disease progression and therapy resistance in triple negative breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Rationale and design of the prevention of paclitaxel-related neurological side effects with lithium trial - Protocol of a multicenter, randomized, double-blind, placebo- controlled proof-of-concept phase-2 clinical trial.Frontiers in medicine · 2022Article
- Biomarkers of Chemotherapy-Induced Peripheral Neuropathy: Current Status and Future Directions.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Functional Interaction between Transient Receptor Potential V4 Channel and Neuronal Calcium Sensor 1 and the Effects of Paclitaxel.Molecular pharmacology · 2021Article
- Targeting p130Cas- and microtubule-dependent MYC regulation sensitizes pancreatic cancer to ERK MAPK inhibition.Cell reports · 2021Article
- Pharmacological rescue of cognitive function in a mouse model of chemobrain.Molecular neurodegeneration · 2021Article
- Comprehensive somatosensory and neurological phenotyping of NCS1 knockout mice.Scientific reports · 2021Article
- Adjuvant role of a T-type calcium channel blocker, TTA-A2, in lung cancer treatment with paclitaxel.Cancer drug resistance (Alhambra, Calif.) · 2021Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Paclitaxel (Taxol) is a well established chemotherapeutic agent for the treatment of solid tumors, but it is limited in its usefulness by the frequent induction of peripheral neuropathy. We found that prolonged exposure of a neuroblastoma cell line and primary rat dorsal root ganglia with therapeutic concentrations of Taxol leads to a reduction in inositol trisphosphate (InsP(3))-mediated Ca(2+) signaling. We also observed a Taxol-specific reduction in neuronal calcium sensor 1 (NCS-1) protein levels, a known modulator of InsP(3) receptor (InsP(3)R) activity. This reduction was also found in peripheral neuronal tissue from Taxol treated animals. We further observed that short hairpin RNA-mediated NCS-1 knockdown had a similar effect on phosphoinositide-mediated Ca(2+) signaling. When NCS-1 protein levels recovered, so did InsP(3)-mediated Ca(2+) signaling. Inhibition of the Ca(2+)-activated protease mu-calpain prevented alterations in phosphoinositide-mediated Ca(2+) signaling and NCS-1 protein levels. We also found that NCS-1 is readily degraded by mu-calpain in vitro and that mu-calpain activity is increased in Taxol but not vehicle-treated cells. From these results, we conclude that prolonged exposure to Taxol activates mu-calpain, which leads to the degradation of NCS-1, which, in turn, attenuates InsP(3)mediated Ca(2+) signaling. These findings provide a previously undescribed approach to understanding and treating Taxol-induced peripheral neuropathy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.