PMID- 12482470
OWN - NLM
STAT- MEDLINE
DCOM- 20030429
LR  - 20190922
IS  - 0022-3956 (Print)
IS  - 0022-3956 (Linking)
VI  - 37
IP  - 1
DP  - 2003 Jan-Feb
TI  - Differential effects of fluoxetine and imipramine on the phosphorylation of the 
      transcription factor CREB and cell-viability.
PG  - 53-9
AB  - It has been shown that antidepressants increase the expression of CREB 
      (cAMP-response-element-binding-protein) and BDNF (brain derived neurotrophic 
      factor) in vivo. Apparently inconsistent to these survival-promoting properties 
      for many years antidepressants are known to induce apoptosis in various cell 
      types in vitro. In the present study we evaluated if the antidepressants 
      imipramine and fluoxetine are capable to influence the translational expression 
      and phosphorylation of CREB (pCREB) in cells known to be apoptosis-inducible by 
      antidepressants. We therefore used jurkat cells and quantified apoptosis via 
      propidiumiodid-staining and FACS-analysis. CREB-expression and -phosphorylation 
      was quantified via western blot. Both antidepressants induced apoptosis within 24 
      h. Fluoxetin starts to induce significant apoptosis at a concentration of 20 
      microM, whereas imipramine at 100 microM. At these concentrations both 
      antidepressants also increased the phosphorylation of CREB within 6 h. But even 
      in concentrations to low to induce apoptosis both antidepressants still increased 
      CREB-phosphorylation. Treating cells with lowest concentrations only imipramine 
      revealed an increase of CREB-phosphorylation after long-time treatment over 3 
      weeks. In all experiments overall CREB-expression remained unchanged. In 
      conclusion our experiments indicate that antidepressants are capable to increase 
      CREB-phosphorylation without induction of apoptosis depending on concentration 
      and duration of treatment. We further assume that antidepressants induce 
      CREB-phosphorylation via signal transduction pathways that are different from 
      those inducing apoptosis.
FAU - Koch, Jakob M
AU  - Koch JM
AD  - Department of Psychiatry, Christian-Albrecht-University Kiel, 24105 Kiel, 
      Germany. jkoch@psychiatry,uni-kiel.de
FAU - Kell, Susanne
AU  - Kell S
FAU - Aldenhoff, Josef B
AU  - Aldenhoff JB
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 01K63SUP8D (Fluoxetine)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
MH  - Antidepressive Agents, Second-Generation/*pharmacology
MH  - Antidepressive Agents, Tricyclic/*pharmacology
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Cell Survival/drug effects/radiation effects
MH  - Cyclic AMP Response Element-Binding Protein/drug effects/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Fluoxetine/*pharmacology
MH  - Humans
MH  - Imipramine/*pharmacology
MH  - Jurkat Cells
MH  - Phosphorylation/drug effects
MH  - Time Factors
EDAT- 2002/12/17 04:00
MHDA- 2003/04/30 05:00
CRDT- 2002/12/17 04:00
PHST- 2002/12/17 04:00 [pubmed]
PHST- 2003/04/30 05:00 [medline]
PHST- 2002/12/17 04:00 [entrez]
AID - S0022395602000614 [pii]
AID - 10.1016/s0022-3956(02)00061-4 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2003 Jan-Feb;37(1):53-9. doi: 10.1016/s0022-3956(02)00061-4.