Role of satellite cell-derived l-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

Kiya, Tamotsu; Kawamata, Tomoyuki; Namiki, Akiyoshi; Yamakage, Michiaki

doi:10.1016/j.neuroscience.2010.11.046

Cited by 31 publications

(22 citation statements)

References 29 publications

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“…While recent reports suggest paclitaxel acts directly on axons to reduce axon length (Yang et al, 2009) and impair outgrowth (Gornstein and Schwarz, 2017), it is not yet established whether paclitaxel directly impacts sensory axons to cause degeneration, or whether degeneration represents an indirect consequence of paclitaxel affecting other components of the sensory circuitry (Jin et al, 2008; Kiya et al, 2011; Li et al, 2014; Peters et al, 2007a; Peters et al, 2007b; Yang et al, 2009; Zhang et al, 2012). To determine the subcellular site of action for paclitaxel-induced degeneration, we introduced paclitaxel (30 nM) into the media surrounding either cell body or distal axon compartments of E15 DRG sensory neurons in compartmented cultures, and analyzed paclitaxel-induced axonal fragmentation, a direct readout of degeneration (Sasaki et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration

Pease-Raissi

Pazyra-Murphy

et al. 2017

Neuron

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Summary Chemotherapy induced peripheral neuropathy (CIPN) is a debilitating side effect of many cancer treatments. The hallmark of CIPN is degeneration of long axons required for transmission of sensory information; axonal degeneration causes impaired tactile sensation and persistent pain. Currently the molecular mechanisms of CIPN are not understood, and there are no available treatments. Here we show that the chemotherapeutic agent paclitaxel triggers CIPN by altering IP3 receptor phosphorylation and intracellular calcium flux, and activating calcium-dependent calpain proteases. Concomitantly paclitaxel impairs axonal trafficking of RNA-granules and reduces synthesis of Bclw (bcl2l2), a Bcl2 family member that binds IP3R1 and restrains axon degeneration. Surprisingly, Bclw or a stapled peptide corresponding to the Bclw BH4 domain interact with axonal IP3R1 and prevent paclitaxel-induced degeneration, while Bcl2 and BclxL cannot do so. Together these data identify a Bclw-IP3R1-dependent cascade that causes axon degeneration, and suggest Bclw-mimetics could provide effective therapy to prevent CIPN.

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Section: Resultsmentioning

confidence: 99%

Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration

Pease-Raissi

Pazyra-Murphy

et al. 2017

Neuron

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“…In addition, we tested whether the transcription level of d ‐3‐phosphoglycerate dehydrogenase (3PGDH) was affected by paclitaxel or cisplatin treatment. 3PGDH is the enzyme of the first committed step of l ‐serine biosynthesis and has been shown in a rat model to decrease as a result of paclitaxel treatment (26). Our results in cells showed that 3PGDH message levels did not change as a result of paclitaxel or cisplatin treatment (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

Neurotoxic 1‐deoxysphingolipids and paclitaxel‐induced peripheral neuropathy

et al. 2015

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Peripheral neuropathy is a major doselimiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses L-alanine instead of L-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 mM) and cisplatin (250 nM, 1 mM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P < 0.05). We also tested whether there is an association between peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C 24 (P < 0.05), with the strongest association being with motor neuropathy (P < 0.001). Our data from cells and from patients with breast cancer suggest that 1-deoxysphingolipids, the very-long-chain in particular, play a role as molecular intermediates of paclitaxel-induced peripheral neuropathy.-Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. FASEB J. 29, 4461-4472 (2015). www.fasebj.org

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“…We used the method described by Kiya et al [9]. Rats were anesthetized with 10% chloral hydrate (500 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

Improvement in Regional CBF by L-Serine Contributes to Its Neuroprotective Effect in Rats after Focal Cerebral Ischemia

Ren

Ren²,

Jiang

et al. 2013

PLoS ONE

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To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF). Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1) reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2) improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3) increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca2+-activated K+ channels on the cerebral blood vessel endothelium.

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Role of satellite cell-derived l-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

Cited by 31 publications

References 29 publications

Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration

Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration

Neurotoxic 1‐deoxysphingolipids and paclitaxel‐induced peripheral neuropathy

Improvement in Regional CBF by L-Serine Contributes to Its Neuroprotective Effect in Rats after Focal Cerebral Ischemia

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