コンテンツへスキップ
Merck
  • Inhibition of adenosine kinase attenuates inflammation and neurotoxicity in traumatic optic neuropathy.

Inhibition of adenosine kinase attenuates inflammation and neurotoxicity in traumatic optic neuropathy.

Journal of neuroimmunology (2014-12-03)
Saif Ahmad, Nehal M Elsherbiny, Kanchan Bhatia, Ahmed M Elsherbini, Sadanand Fulzele, Gregory I Liou
要旨

Traumatic optic neuropathy (TON) is associated with apoptosis of retinal ganglion cells. Local productions of reactive oxygen species and inflammatory mediators from activated microglial cells have been hypothesized to underlie apoptotic processes. We previously demonstrated that the anti-inflammatory effect of adenosine, through A2A receptor activation had profound protective influence against retinal injury in traumatic optic neuropathy. This protective effect is limited due to rapid cellular re-uptake of adenosine by equilibrative nucleotside transporter-1 (ENT1) or break down by adenosine kinase (AK), the key enzyme in adenosine clearance pathway. Further, the use of adenosine receptors agonists are limited by systemic side effects. Therefore, we seek to investigate the potential role of amplifying the endogenous ambient level of adenosine by pharmacological inhibition of AK. We tested our hypothesis by comparing TON-induced retinal injury in mice with and without ABT-702 treatment, a selective AK inhibitor (AKI). The retinal-protective effect of ABT-702 was demonstrated by significant reduction of Iba-1, ENT1, TNF-α, IL-6, and iNOS/nNOS protein or mRNA expression in TON as revealed by western blot and real time PCR. TON-induced superoxide anion generation and nitrotyrosine expression were reduced in ABT-702 treated mice retinal sections as determined by immunoflourescence. In addition, ABT-702 attenuated p-ERK1/2 and p-P38 activation in LPS induced activated mouse microglia cells. The results of the present investigation suggested that ABT-702 had a protective role against marked TON-induced retinal inflammation and damage by augmenting the endogenous therapeutic effects of site- and event-specific accumulation of extracellular adenosine.

材料
製品番号
ブランド
製品内容

Sigma-Aldrich
フッ化ナトリウム, ACS reagent, ≥99%
Sigma-Aldrich
L-グルタミン, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
フェニルメチルスルホニルフルオリド, ≥98.5% (GC)
Sigma-Aldrich
L-グルタミン, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
アデノシン, ≥99%
Sigma-Aldrich
エチレンジアミン四酢酸 溶液, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
SAFC
L-グルタミン
Sigma-Aldrich
エチレンジアミン四酢酸, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
エチレンジアミン四酢酸, 99.995% trace metals basis
Sigma-Aldrich
フェニルメチルスルホニルフルオリド, ≥99.0% (T)
Sigma-Aldrich
フッ化ナトリウム, ReagentPlus®, ≥99%
Sigma-Aldrich
フッ化ナトリウム, 99.99% trace metals basis
Sigma-Aldrich
L-グルタミン, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
アデノシン, suitable for cell culture, BioReagent
Sigma-Aldrich
フルオロセイン(遊離酸), Dye content 95 %
Sigma-Aldrich
エチレンジアミン四酢酸, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
フッ化ナトリウム, anhydrous, powder, 99.99% trace metals basis
Sigma-Aldrich
フッ化ナトリウム, puriss., meets analytical specification of Ph. Eur., BP, USP, 98.5-100.5% (calc. to the dried substance)
Sigma-Aldrich
フッ化ナトリウム溶液
Sigma-Aldrich
フッ化ナトリウム, BioReagent, suitable for insect cell culture, ≥99%
Sigma-Aldrich
L-グルタミン, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
アデノシン
Sigma-Aldrich
L-グルタミン
Sigma-Aldrich
エチレンジアミン四酢酸, anhydrous, BioUltra, ≥99% (titration)
Sigma-Aldrich
エチレンジアミン四酢酸 二ナトリウム塩 溶液, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Sigma-Aldrich
フッ化ナトリウム, BioXtra, ≥99%
Sigma-Aldrich
エチレンジアミン四酢酸, purified grade, ≥98.5%, powder
Sigma-Aldrich
フッ化ナトリウム0.5 M 溶液
Supelco
Fluoride ion solution for ISE, 0.1 M F-, analytical standard (for ion-selective electrodes)
Sigma-Aldrich
エチレンジアミン四酢酸, ≥98.0% (KT)