Linked Life Data

21120605

Source:http://linkedlifedata.com/resource/pubmed/id/21120605

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-19
pubmed:abstractText
The in vitro effects of antidepressant drugs on mitochondrial function were investigated in a CHO?(2)SPAP cell line used previously to determine the effects of antidepressants on gene transcription (Abdel-Razaq et al., Biochem Pharmacol 73:1995-2003, 2007) and in rat heart isolated mitochondria. Apoptotic effects of clomipramine (CLOM), desipramine (DMI) and of norfluoxetine (NORF, the active metabolite of fluoxetine), on cellular viability were indicated by morphological changes and concentration-dependent increases in caspase-3 activity in CHO cells after 18 h exposure to CLOM, DMI and NORF. However, tianeptine (TIAN) was without effect. CLOM and NORF both reduced integrated mitochondrial function as shown by marked reductions in membrane potential (MMP) in mitochondria isolated from rat hearts. DMI also showed a similar but smaller effect, whereas, TIAN did not elicit any significant change in MMP. Moreover, micromolar concentrations of CLOM, DMI and NORF caused significant inhibitions of the activities of mitochondrial complexes (I, II/III and IV). The inhibitory effects on complex IV activity were most marked. TIAN inhibited only complex I activity at concentrations in excess of 20 ?M. The observed inhibitory effects of antidepressants on the mitochondrial complexes were accompanied by a significant decrease in the mitochondrial state-3 respiration at concentrations above 10 ?M. The results demonstrate that the apoptotic cell death observed in antidepressant-treated cells could be due to disruption of mitochondrial function resulting from multiple inhibition of mitochondrial enzyme complexes. The possibility that antimitochondrial actions of antidepressants could provide a potentially protective pre-conditioning effect is discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1573-6903
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
327-38
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The effects of antidepressants on mitochondrial function in a model cell system and isolated mitochondria.
pubmed:affiliation
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, The Hashemite University, Zarqa, Jordan. wabdelrazaq@hu.edu.jo
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't