PMID- 16942526
OWN - NLM
STAT- MEDLINE
DCOM- 20061206
LR  - 20171016
IS  - 1743-6095 (Print)
IS  - 1743-6095 (Linking)
VI  - 3
IP  - 5
DP  - 2006 Sep
TI  - Brain-derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway 
      to promote neurite growth in the major pelvic ganglion of the rat: part I.
PG  - 815-820
LID - S1743-6095(15)31398-9 [pii]
LID - 10.1111/j.1743-6109.2006.00291.x [doi]
AB  - INTRODUCTION: Identification of the molecular mechanism of cavernous nerve 
      regeneration is essential for future development of neuroprotective and 
      regenerative strategies. AIM: To identify specific signal transduction pathway(s) 
      associated with brain-derived neurotrophic factor (BDNF) enhanced cavernous nerve 
      regeneration in an in vitro model. MATERIALS AND METHODS: Using 6-month-old male 
      Fisher rats, inhibitors of four candidate signaling pathways were added to 
      BDNF-treated explant cultures of major pelvic ganglia with attached cavernous 
      nerve fragments. Study groups comprised of controls, BDNF alone at 50 ng/mL, or 
      BDNF 50 ng/mL and inhibitors against MEK, PI3-K, PKA, and JAK/STAT pathways at 
      increasing concentrations. MAIN OUTCOME MEASURE: The maximal neurite length for 
      each tissue culture was measured and the mean maximal length +/- standard 
      deviation was determined for all groups at 24, 36, and 48 hours. RESULTS: The 
      JAK/STAT specific inhibitor AG490 significantly reduced BDNF-enhanced neurite 
      growth. Maximum neurite lengths at 24, 36, and 48 hours for BDNF 50 ng/mL treated 
      groups were 182.3, 348.1, and 528.1 microm, compared with AG490 at 25 microM 
      (86.4, 165.1, 278.3 microm), 50 microM (78.8, 151.7, 235.3 microm), and 100 
      microM (71.83, 107.0, 219.6 microm) (P < 0.05). Neurite measures for BDNF with 25 
      and 50 microM U0126 (MEK pathway) were reduced to 402.0 and 424.3 microm at 48 
      hours, respectively (P < 0.05), likely reflecting an accessory molecular pathway. 
      A similar observation was made for 100 uM LY294002 (PI3-K). No difference was 
      observed for PKA inhibition. CONCLUSION: The JAK/STAT pathway is the major 
      signal-transduction pathway of BDNF-enhanced cavernous nerve growth in an in 
      vitro rat model.
FAU - Bella, Anthony J
AU  - Bella AJ
AD  - Department of Urology, University of California San Francisco, San Francisco, CA, 
      USA. Electronic address: abella@urology.ucsf.edu.
FAU - Lin, Guiting
AU  - Lin G
AD  - Department of Urology, University of California San Francisco, San Francisco, CA, 
      USA.
FAU - Tantiwongse, Kavirach
AU  - Tantiwongse K
AD  - Department of Urology, University of California San Francisco, San Francisco, CA, 
      USA.
FAU - Garcia, Maurice
AU  - Garcia M
AD  - Department of Urology, University of California San Francisco, San Francisco, CA, 
      USA.
FAU - Lin, Ching-Schwun
AU  - Lin CS
AD  - Department of Urology, University of California San Francisco, San Francisco, CA, 
      USA.
FAU - Brant, William
AU  - Brant W
AD  - Department of Urology, University of California San Francisco, San Francisco, CA, 
      USA.
FAU - Lue, Tom F
AU  - Lue TF
AD  - Department of Urology, University of California San Francisco, San Francisco, CA, 
      USA.
LA  - eng
GR  - 2R01-DK-45370/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Sex Med
JT  - The journal of sexual medicine
JID - 101230693
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (STAT Transcription Factors)
RN  - EC 2.7.10.2 (Jak1 protein, rat)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Chromatography, High Pressure Liquid/methods
MH  - Ganglia, Parasympathetic/*metabolism
MH  - In Vitro Techniques
MH  - Janus Kinase 1/*metabolism
MH  - Male
MH  - Neurites/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Ganglion Cells/*metabolism
MH  - STAT Transcription Factors/*metabolism
MH  - Signal Transduction
EDAT- 2006/09/01 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/09/01 09:00
PHST- 2006/09/01 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/09/01 09:00 [entrez]
AID - S1743-6095(15)31398-9 [pii]
AID - 10.1111/j.1743-6109.2006.00291.x [doi]
PST - ppublish
SO  - J Sex Med. 2006 Sep;3(5):815-820. doi: 10.1111/j.1743-6109.2006.00291.x.