PMID- 29243095
OWN - NLM
STAT- MEDLINE
DCOM- 20180815
LR  - 20181202
IS  - 1567-2387 (Electronic)
IS  - 1567-2379 (Linking)
VI  - 49
IP  - 1
DP  - 2018 Feb
TI  - Ca(2+)-CaMKKbeta pathway is required for adiponectin-induced secretion in rat 
      submandibular gland.
PG  - 99-110
LID - 10.1007/s10735-017-9750-3 [doi]
AB  - Adiponectin functions as a promoter of saliva secretion in rat submandibular 
      gland via activation of adenosine monophosphate-activated protein kinase (AMPK) 
      and increased paracellular permeability. Ca(2+) mobilization is the primary 
      signal for fluid secretion in salivary acinar cells. However, whether 
      intracellular Ca(2+) mobilization is involved in adiponectin-induced salivary 
      secretion is unknown. Here, we found that full-length adiponectin (fAd) increased 
      intracellular Ca(2+) and saliva secretion in submandibular glands. Pre-perfusion 
      with ethylene glycol-bis (2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) 
      combined with thapsigargin (TG), an endoplasmic reticulum Ca(2+)-ATPase 
      inhibitor, abolished fAd-induced salivary secretion, AMPK phosphorylation, and 
      enlarged tight junction (TJ) width. Furthermore, in cultured SMG-C6 cells, 
      co-pretreatment with EGTA and TG suppressed fAd-decreased transepithelial 
      electrical resistance and increased 4-kDa FITC-dextran flux responses. Moreover, 
      fAd increased phosphorylation of calcium/calmodulin-dependent protein kinase 
      (CaMKKbeta), a major kinase that is activated by elevated levels of intracellular 
      Ca(2+), but not liver kinase B1 phosphorylation. Pre-perfusion of the isolated 
      gland with STO-609, an inhibitor of CaMKKbeta, abolished fAd-induced salivary 
      secretion, AMPK activation, and enlarged TJ width. CaMKKbeta shRNA suppressed, 
      whereas CaMKKbeta re-expression rescued fAd-increased paracellular permeability. 
      Taken together, these results indicate that adiponectin induced Ca(2+) modulation 
      in rat submandibular gland acinar cells. Ca(2+)-CaMKKbeta pathway is required for 
      adiponectin-induced secretion through mediating AMPK activation and increase in 
      paracellular permeability in rat submandibular glands.
FAU - Ding, Chong
AU  - Ding C
AUID- ORCID: 0000-0002-1834-4421
AD  - Center Laboratory, Peking University School and Hospital of Stomatology, Beijing, 
      100081, People's Republic of China.
FAU - Du, Zhi-Hao
AU  - Du ZH
AD  - Department of Oral and Maxillofacial Surgery, Peking University School and 
      Hospital of Stomatology, 22 Zhongguancun South Street, Haidian District, Beijing, 
      100081, People's Republic of China.
FAU - Li, Sheng-Lin
AU  - Li SL
AD  - Center Laboratory, Peking University School and Hospital of Stomatology, Beijing, 
      100081, People's Republic of China.
FAU - Wu, Li-Ling
AU  - Wu LL
AD  - Department of Physiology and Pathophysiology, Peking University School of Basic 
      Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry 
      of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, 38 
      Xueyuan Road, Haidian District, Beijing, 100191, People's Republic of China. 
      pathophy@bjmu.edu.cn.
FAU - Yu, Guang-Yan
AU  - Yu GY
AD  - Department of Oral and Maxillofacial Surgery, Peking University School and 
      Hospital of Stomatology, 22 Zhongguancun South Street, Haidian District, Beijing, 
      100081, People's Republic of China. gyyu@263.net.
LA  - eng
GR  - 81771088/National Natural Science Foundation of China/
GR  - 81200799/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20171214
PL  - Netherlands
TA  - J Mol Histol
JT  - Journal of molecular histology
JID - 101193653
RN  - 0 (Adiponectin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
RN  - EC 2.7.4.3 (Adenylate Kinase)
SB  - IM
MH  - Acinar Cells/metabolism
MH  - Adenylate Kinase/metabolism
MH  - Adiponectin/*pharmacology
MH  - Animals
MH  - Calcium Signaling
MH  - Calcium-Calmodulin-Dependent Protein Kinase Kinase/*metabolism
MH  - Rats
MH  - Saliva/metabolism
MH  - Submandibular Gland/*metabolism
OTO - NOTNLM
OT  - Adenosine monophosphate-activated protein kinase
OT  - Adiponectin
OT  - Calcium
OT  - Calcium/calmodulin-dependent protein kinase
OT  - Secretion
OT  - Submandibular gland
EDAT- 2017/12/16 06:00
MHDA- 2018/08/16 06:00
CRDT- 2017/12/16 06:00
PHST- 2017/11/13 00:00 [received]
PHST- 2017/12/05 00:00 [accepted]
PHST- 2017/12/16 06:00 [pubmed]
PHST- 2018/08/16 06:00 [medline]
PHST- 2017/12/16 06:00 [entrez]
AID - 10.1007/s10735-017-9750-3 [pii]
AID - 10.1007/s10735-017-9750-3 [doi]
PST - ppublish
SO  - J Mol Histol. 2018 Feb;49(1):99-110. doi: 10.1007/s10735-017-9750-3. Epub 2017 
      Dec 14.