Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-1-26
pubmed:abstractText
Thiol redox state (TRS) is an important parameter to reflect intracellular oxidative stress and is associated with various normal and abnormal biochemical processes. Agents that can be used to increase intracellular TRS will be valuable tools in TRS-related research. Glutathione reductase (GR) is a critical enzyme in the homeostasis of TRS. The enzyme catalyzes the reduction of GSSG to GSH to maintain a high GSH:GSSG ratio. Inhibition of the enzyme can be used to increase TRS. Despite the reports of various GR inhibitors, N,N-bis(2-chloroethyl)-N-nitrosourea, an anticancer drug with IC(50) = 647 microm against yeast GR, remains the most commonly used GR inhibitor in the literature. However, the toxicity caused by nonspecific interactions, as well as inhibition of DNA synthesis, complicates the use of N,N-bis(2-chloroethyl)-N-nitrosourea as a GR inhibitor. We report 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as a novel irreversible GR inhibitor. 2-AAPA was prepared by one-step synthesis from commercially available reagents. The K(i) and k(inact) of 2-AAPA against yeast GR were determined to be 56 microm and 0.1 min(-1), respectively. At the concentration that produced >80% yeast GR inhibition, 2-AAPA showed no inhibition against glutamylcysteine synthetase, glutathione synthetase, catalase, and superoxide dismutase, but minimal inhibition against glutathione S-transferase and glutathione peroxidase. In CV-1 cells, 2-AAPA (0.1 mm) produced 97% GR inhibition, 25% GSH reduction, and a 5-fold increase in GSSG in 20 min. The compound can be a useful tool in TRS-related research.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-10604861, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-10769127, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-11708927, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-11854154, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-12609664, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-12939310, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-14033211, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-14985909, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-15234979, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-15537352, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-15694268, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-15788230, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-15792952, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-15866059, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-15896810, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-15927968, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-1597863, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-15998251, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16078841, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16160061, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16246123, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16261319, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16337153, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16430879, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16447283, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16527239, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16863996, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-16910673, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-1704137, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-17382203, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-17431186, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-17554778, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-1975172, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-1980497, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-1989629, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-2297827, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-2404494, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-2644959, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-3338461, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-5353890, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-6444211, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-8068046, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-8161349, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-8536691, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-8626496, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-8691487, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-9268306, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-942051, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-9498806, http://linkedlifedata.com/resource/pubmed/commentcorrection/19049979-9986706
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2729-37
pubmed:dateRevised
2010-9-22
pubmed:meshHeading
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