PMID- 21371533
OWN - NLM
STAT- MEDLINE
DCOM- 20120316
LR  - 20220408
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 181
DP  - 2011 May 5
TI  - Caffeine and uric acid mediate glutathione synthesis for neuroprotection.
PG  - 206-15
LID - 10.1016/j.neuroscience.2011.02.047 [doi]
AB  - Several lines of epidemiological studies have indicated that caffeine consumption 
      and plasma uric acid (UA) level were negatively correlated with the incidence of 
      some neurodegenerative diseases. We report here a novel mechanism by which these 
      purine derivatives increase neuronal glutathione (GSH) synthesis. Intraperitoneal 
      injection of caffeine or UA into male C57BL/6 mice significantly increased total 
      GSH levels in the hippocampus. Neither SCH58261, an adenosine A2A receptor 
      antagonist, nor rolipram, a phosphodiesterase-4 inhibitor, increased GSH levels. 
      Pretreatment with allopurinol, a drug to inhibit UA production, did not change 
      the GSH level in the caffeine-treated mice. Hippocampal CA1 pyramidal neurons 
      treated with caffeine or UA were resistant to oxidant exposure in the slice 
      culture experiments. In experiments with the SH-SY5Y cell line, cysteine uptake 
      was sodium-dependent and pretreatment with caffeine or UA increased cysteine 
      uptake significantly as compared with the control conditions. Slice culture 
      experiments using the hippocampus also showed increased cysteine and GSH contents 
      after the treatment with caffeine or UA. Immunohistochemical analysis showed 
      increased GSH levels in the hippocampal excitatory amino acid carrier-1 
      (EAAC1)-positive neurons of mice treated with caffeine or UA. These findings 
      suggest that purine derivatives caffeine and UA induce neuronal GSH synthesis by 
      promoting cysteine uptake, leading to neuroprotection.
CI  - Copyright (c) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Aoyama, K
AU  - Aoyama K
AD  - Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, 
      Itabashi, Tokyo 173-8501, Japan.
FAU - Matsumura, N
AU  - Matsumura N
FAU - Watabe, M
AU  - Watabe M
FAU - Wang, F
AU  - Wang F
FAU - Kikuchi-Utsumi, K
AU  - Kikuchi-Utsumi K
FAU - Nakaki, T
AU  - Nakaki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110301
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Neuroprotective Agents)
RN  - 268B43MJ25 (Uric Acid)
RN  - 3G6A5W338E (Caffeine)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Caffeine/*pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - Glutathione/*agonists/biosynthesis
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Organ Culture Techniques
MH  - Oxidative Stress/*drug effects/physiology
MH  - Uric Acid/*pharmacology/therapeutic use
EDAT- 2011/03/05 06:00
MHDA- 2012/03/17 06:00
CRDT- 2011/03/05 06:00
PHST- 2010/10/30 00:00 [received]
PHST- 2011/02/14 00:00 [revised]
PHST- 2011/02/18 00:00 [accepted]
PHST- 2011/03/05 06:00 [entrez]
PHST- 2011/03/05 06:00 [pubmed]
PHST- 2012/03/17 06:00 [medline]
AID - S0306-4522(11)00217-X [pii]
AID - 10.1016/j.neuroscience.2011.02.047 [doi]
PST - ppublish
SO  - Neuroscience. 2011 May 5;181:206-15. doi: 10.1016/j.neuroscience.2011.02.047. 
      Epub 2011 Mar 1.