PMID- 24958862
OWN - NLM
STAT- MEDLINE
DCOM- 20140915
LR  - 20211203
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 111
IP  - 27
DP  - 2014 Jul 8
TI  - Role of cysteinyl leukotriene signaling in a mouse model of noise-induced 
      cochlear injury.
PG  - 9911-6
LID - 10.1073/pnas.1402261111 [doi]
AB  - Noise-induced hearing loss is one of the most common types of sensorineural 
      hearing loss. In this study, we examined the expression and localization of 
      leukotriene receptors and their respective changes in the cochlea after hazardous 
      noise exposure. We found that the expression of cysteinyl leukotriene type 1 
      receptor (CysLTR1) was increased until 3 d after noise exposure and enhanced 
      CysLTR1 expression was mainly observed in the spiral ligament and the organ of 
      Corti. Expression of 5-lipoxygenase was increased similar to that of CysLTR1, and 
      there was an accompanying elevation of CysLT concentration. Posttreatment with 
      leukotriene receptor antagonist (LTRA), montelukast, for 4 consecutive days after 
      noise exposure significantly decreased the permanent threshold shift and also 
      reduced the hair cell death in the cochlea. Using RNA-sequencing, we found that 
      the expression of matrix metalloproteinase-3 (MMP-3) was up-regulated after noise 
      exposure, and it was significantly inhibited by montelukast. Posttreatment with a 
      MMP-3 inhibitor also protected the hair cells and reduced the permanent threshold 
      shift. These findings suggest that acoustic injury up-regulated CysLT signaling 
      in the cochlea and cochlear injury could be attenuated by LTRA through regulation 
      of MMP-3 expression. This study provides mechanistic insights into the role of 
      CysLTs signaling in noise-induced hearing loss and the therapeutic benefit of 
      LTRA.
FAU - Park, Jung-Sub
AU  - Park JS
AD  - Department of Pharmacology,Department of Otolaryngology,Neuroscience Graduate 
      Program, Department of Biological Sciences,Chronic Inflammatory Disease Research 
      Center, and.
FAU - Kang, Seo-Jun
AU  - Kang SJ
AD  - Department of Pharmacology,Neuroscience Graduate Program, Department of 
      Biological Sciences,Chronic Inflammatory Disease Research Center, and.
FAU - Seo, Mi-Kyoung
AU  - Seo MK
AD  - Chronic Inflammatory Disease Research Center, andDepartment of Physiology, Ajou 
      University School of Medicine, Yeongtong-gu, Suwon 443-380, Korea.
FAU - Jou, Ilo
AU  - Jou I
AD  - Department of Pharmacology,Neuroscience Graduate Program, Department of 
      Biological Sciences,Chronic Inflammatory Disease Research Center, and.
FAU - Woo, Hyun Goo
AU  - Woo HG
AD  - Chronic Inflammatory Disease Research Center, andDepartment of Physiology, Ajou 
      University School of Medicine, Yeongtong-gu, Suwon 443-380, Korea.
FAU - Park, Sang Myun
AU  - Park SM
AD  - Department of Pharmacology,Neuroscience Graduate Program, Department of 
      Biological Sciences,Chronic Inflammatory Disease Research Center, and 
      sangmyun@ajou.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140623
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Acetates)
RN  - 0 (Cyclopropanes)
RN  - 0 (Leukotriene Antagonists)
RN  - 0 (Leukotrienes)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Leukotriene)
RN  - 0 (Sulfides)
RN  - 0 (cysteinyl-leukotriene)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - K848JZ4886 (Cysteine)
RN  - LRF7RW46ID (leukotriene D4 receptor)
RN  - MHM278SD3E (montelukast)
SB  - IM
MH  - Acetates/therapeutic use
MH  - Animals
MH  - Cochlea/*injuries
MH  - Cyclopropanes
MH  - Cysteine/*metabolism
MH  - *Disease Models, Animal
MH  - Gene Expression Profiling
MH  - Leukotriene Antagonists/therapeutic use
MH  - Leukotrienes/*metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Mice
MH  - Noise/*adverse effects
MH  - Quinolines/therapeutic use
MH  - Receptors, Leukotriene/drug effects
MH  - *Signal Transduction
MH  - Sulfides
MH  - Wounds and Injuries/drug therapy/etiology
PMC - PMC4103370
COIS- The authors declare no conflict of interest.
EDAT- 2014/06/25 06:00
MHDA- 2014/09/16 06:00
PMCR- 2015/01/08
CRDT- 2014/06/25 06:00
PHST- 2014/06/25 06:00 [entrez]
PHST- 2014/06/25 06:00 [pubmed]
PHST- 2014/09/16 06:00 [medline]
PHST- 2015/01/08 00:00 [pmc-release]
AID - 1402261111 [pii]
AID - 201402261 [pii]
AID - 10.1073/pnas.1402261111 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9911-6. doi: 
      10.1073/pnas.1402261111. Epub 2014 Jun 23.