PMID- 21151481
OWN - NLM
STAT- MEDLINE
DCOM- 20110427
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 11
DP  - 2010 Nov 8
TI  - A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 
      cells: translation initiation [corrected] factor eIF4AI.
PG  - e15430
LID - 10.1371/journal.pone.0015430 [doi]
LID - e15430
AB  - BACKGROUND: Minocycline, a second-generation tetracycline antibiotic, has 
      potential activity for the treatment of several neurodegenerative and psychiatric 
      disorders. However, its mechanisms of action remain to be determined. 
      METHODOLOGY/PRINCIPAL FINDINGS: We found that minocycline, but not tetracycline, 
      significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in 
      PC12 cells, in a concentration dependent manner. Furthermore, we found that the 
      endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP3) receptors and 
      several common signaling molecules (PLC-gamma, PI3K, Akt, p38 MAPK, c-Jun N-terminal 
      kinase (JNK), mammalian target of rapamycin (mTOR), and Ras/Raf/ERK/MAPK 
      pathways) might be involved in the active mechanism of minocycline. Moreover, we 
      found that a marked increase of the eukaryotic translation initiation factor 
      eIF4AI protein by minocycline, but not tetracycline, might be involved in the 
      active mechanism for NGF-induced neurite outgrowth. CONCLUSIONS/SIGNIFICANCE: 
      These findings suggest that eIF4AI might play a role in the novel mechanism of 
      minocycline. Therefore, agents that can increase eIF4AI protein would be novel 
      therapeutic drugs for certain neurodegenerative and psychiatric diseases.
FAU - Hashimoto, Kenji
AU  - Hashimoto K
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba, Japan. hashimoto@faculty.chiba-u.jp
FAU - Ishima, Tamaki
AU  - Ishima T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101108
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Macrocyclic Compounds)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Oxazoles)
RN  - 0 (Tetracyclines)
RN  - 0 (xestospongin C)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.11.1 (raf Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.7.- (Eukaryotic Initiation Factor-4A)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - FYY3R43WGO (Minocycline)
RN  - N12000U13O (Doxycycline)
SB  - IM
EIN - PLoS One. 2010;5(12) Doi: 10.1371/annotation/afc0a9a2-01c0-4e58-8d69-e0ed4ff953fa
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Blotting, Western
MH  - Dose-Response Relationship, Drug
MH  - Doxycycline/pharmacology
MH  - Drug Synergism
MH  - Eukaryotic Initiation Factor-4A/genetics/metabolism
MH  - Immunohistochemistry
MH  - Inositol 1,4,5-Trisphosphate Receptors/antagonists & inhibitors/metabolism
MH  - Macrocyclic Compounds/pharmacology
MH  - Microtubule-Associated Proteins/metabolism
MH  - Minocycline/*pharmacology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Nerve Growth Factor/*pharmacology
MH  - Neurites/*drug effects/physiology
MH  - Oxazoles/pharmacology
MH  - PC12 Cells
MH  - RNA Interference
MH  - Rats
MH  - Signal Transduction/drug effects
MH  - Tetracyclines/pharmacology
MH  - raf Kinases/metabolism
MH  - ras Proteins/metabolism
PMC - PMC2975708
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/12/15 06:00
MHDA- 2011/04/28 06:00
PMCR- 2010/11/08
CRDT- 2010/12/15 06:00
PHST- 2010/08/06 00:00 [received]
PHST- 2010/09/20 00:00 [accepted]
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2011/04/28 06:00 [medline]
PHST- 2010/11/08 00:00 [pmc-release]
AID - PONE-D-10-00422 [pii]
AID - 10.1371/journal.pone.0015430 [doi]
PST - epublish
SO  - PLoS One. 2010 Nov 8;5(11):e15430. doi: 10.1371/journal.pone.0015430.