PMID- 15455741
OWN - NLM
STAT- MEDLINE
DCOM- 20041025
LR  - 20211203
IS  - 0022-3492 (Print)
IS  - 0022-3492 (Linking)
VI  - 75
IP  - 8
DP  - 2004 Aug
TI  - Localization of the NO-cGMP signaling pathway molecules, NOS III-phosphorylation 
      sites, ERK1/2, and Akt/PKB in osteoclasts.
PG  - 1119-25
AB  - BACKGROUND: Nitric oxide (NO) mediates different cellular functions by activating 
      soluble guanylate cyclase (sGC) that converts guanosine-5'-triphosphate (GTP) to 
      cyclic guanosine-3',5'-monophosphate (cGMP). Membrane-bound GCs produce cGMP in 
      response to natriuretic peptides in osteoblasts, but neither the NO-target enzyme 
      sGC, nor the phosphorylation sites of NOS III, nor their regulation by 
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Akt/protein kinase B 
      (Akt/PKB) in osteoclasts have been established. METHODS: Rat molars with 
      periodontium were perfusion- and post-fixed, decalcified, and frozen-sectioned. 
      Free-floating sections were stained using nicotinamide adenine dinucleotide 
      phosphate-diaphorase (NADPH-d) and tartrate-resistant acid phosphatase (TRAP) 
      histochemical techniques and immunoreacted with antisera against NO-synthase 
      (NOS) I-III, NOS III phoshorylated at Thr495, NOS III phoshorylated at Serine1177 
      (Ser1177), ERK1/2, phosphorylated ERK1/2, Akt/PKB, phosphorylated Akt/PKB, sGC 
      (alpha2/beta1), and cGMP. RESULTS: NADPH-d staining and immunostaining of NOS 
      I-III, NOS III phosphorylated at Ser1177, ERK1/2, Akt/PKB, phosphorylated 
      Akt/PKB, sGC (alpha2 and beta1-subunits), and cGMP were detected in osteoclasts. 
      Immunohistochemical reaction products for NOS III phosphorylated at threonine495 
      (Thr495) and phosphorylated ERK1/2 could not be identified in osteoclasts. 
      Comparison of TRAP activity and immunostaining for sGC beta1-subunit revealed 
      that sGC beta1-subunit is only expressed in a sub-population of osteoclasts. 
      CONCLUSIONS: NO is likely to be generated by NOS I and NOS III in osteoclasts. 
      The inconstant expression of NOS II in some osteoclasts may be explained with 
      inducible expression of NOS II upon physiological cell activation. Localization 
      of the sGC alpha2- and beta1-subunits and cGMP in osteoclasts is compatible with 
      an involvement of NO-sGC signaling in the homeostasis of osteoclasts. The 
      phosphorylation site of NOS III at Ser1177 and phosphorylated Akt/PKB are 
      involved in regulation of NO production by NOS III in osteoclasts under basal 
      conditions.
FAU - Korkmaz, Yuksel
AU  - Korkmaz Y
AD  - Department of Operative and Preventive Dentistry and Endodontics, 
      Heinrich-Heine-University, Dusseldorf, Germany.
FAU - Baumann, Michael A
AU  - Baumann MA
FAU - Schroder, Hannsjorg
AU  - Schroder H
FAU - Behrends, Sonke
AU  - Behrends S
FAU - Addicks, Klaus
AU  - Addicks K
FAU - Raab, Wolfgang H M
AU  - Raab WH
FAU - Bloch, Wilhelm
AU  - Bloch W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Periodontol
JT  - Journal of periodontology
JID - 8000345
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Alveolar Process/*cytology/enzymology
MH  - Animals
MH  - Cyclic GMP/biosynthesis
MH  - Guanylate Cyclase/metabolism
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase/*metabolism
MH  - Osteoclasts/*enzymology
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - *Second Messenger Systems
EDAT- 2004/10/01 05:00
MHDA- 2004/10/27 09:00
CRDT- 2004/10/01 05:00
PHST- 2004/10/01 05:00 [pubmed]
PHST- 2004/10/27 09:00 [medline]
PHST- 2004/10/01 05:00 [entrez]
AID - 10.1902/jop.2004.75.8.1119 [doi]
PST - ppublish
SO  - J Periodontol. 2004 Aug;75(8):1119-25. doi: 10.1902/jop.2004.75.8.1119.