PMID- 28674258
OWN - NLM
STAT- MEDLINE
DCOM- 20180502
LR  - 20181202
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 40
IP  - 7
DP  - 2017
TI  - Roles of Transient Receptor Potential Ankyrin 1 in Oxaliplatin-Induced Peripheral 
      Neuropathy.
PG  - 947-953
LID - 10.1248/bpb.b17-00243 [doi]
AB  - Chemotherapy-induced peripheral neuropathy (CIPN), characterized by symptoms of 
      paresthesia, dysesthesia, numbness, and pain, is a common adverse effect of 
      several chemotherapeutic agents, including platinum-based agents, taxanes, and 
      vinca alkaloids. However, no effective prevention or treatment strategies exist 
      for CIPN because the mechanisms underpinning this neuropathy are poorly 
      understood. Recent accumulating evidence suggests that some transient receptor 
      potential (TRP) channels functioning as nociceptors in primary sensory neurons 
      are responsible for CIPN. In this review, we focus on the specific roles of 
      redox-sensitive TRP ankyrin 1 (TRPA1), which was first reported to be a cold 
      nociceptor, in acute cold hypersensitivity induced by oxaliplatin, a 
      platinum-based agent, because it induces a peculiar cold-triggered CIPN during or 
      within hours after its infusion. Oxaliplatin-induced rapid-onset cold 
      hypersensitivity is ameliorated by TRPA1 blockade or deficiency in mice. 
      Consistent with this, oxaliplatin enhances the responsiveness of TRPA1 
      stimulation, but not of TRP melastatin 8 (TRPM8) and TRP vanilloid 1 (TRPV1), in 
      mice and cultured mouse dorsal root ganglion neurons. These responses are 
      mimicked by an oxaliplatin metabolite, oxalate. In human TRPA1 
      (hTRPA1)-expressing cells, oxaliplatin or oxalate causes TRPA1 sensitization to 
      reactive oxygen species (ROS) by inhibiting prolyl hydroxylases (PHDs). 
      Inhibition of PHD-mediated hydroxylation of a proline residue within the 
      N-terminal ankyrin repeat of hTRPA1 endows TRPA1 with cold sensitivity by its 
      sensing of cold-evoked ROS. This review discusses these findings and summarizes 
      the evidence demonstrating that oxaliplatin-induced acute cold hypersensitivity 
      is caused by TRPA1 sensitization to ROS via PHD inhibition, which enables TRPA1 
      to convert ROS signaling into cold sensitivity.
FAU - Nakagawa, Takayuki
AU  - Nakagawa T
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital.
FAU - Kaneko, Shuji
AU  - Kaneko S
AD  - Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, 
      Kyoto University.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Organoplatinum Compounds)
RN  - 0 (TRPA1 Cation Channel)
RN  - 04ZR38536J (Oxaliplatin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*adverse effects
MH  - Humans
MH  - Mice
MH  - Organoplatinum Compounds/*adverse effects
MH  - Oxaliplatin
MH  - Peripheral Nervous System Diseases/*chemically induced
MH  - TRPA1 Cation Channel/*physiology
OTO - NOTNLM
OT  - cold sensitivity
OT  - oxaliplatin
OT  - peripheral neuropathy
OT  - prolyl hydroxylase
OT  - reactive oxygen species
OT  - transient receptor potential ankyrin 1
EDAT- 2017/07/05 06:00
MHDA- 2018/05/03 06:00
CRDT- 2017/07/05 06:00
PHST- 2017/07/05 06:00 [entrez]
PHST- 2017/07/05 06:00 [pubmed]
PHST- 2018/05/03 06:00 [medline]
AID - 10.1248/bpb.b17-00243 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2017;40(7):947-953. doi: 10.1248/bpb.b17-00243.