PMID- 28220552
OWN - NLM
STAT- MEDLINE
DCOM- 20180904
LR  - 20211204
IS  - 1520-6777 (Electronic)
IS  - 0733-2467 (Linking)
VI  - 36
IP  - 8
DP  - 2017 Nov
TI  - Activation of the mTOR dependent signaling pathway underlies ketamine-induced 
      uropathy.
PG  - 1988-1995
LID - 10.1002/nau.23234 [doi]
AB  - AIMS: To investigate the pathogenic role of activation of the mammalian target of 
      the rapamycin (mTOR) in the ketamine induced microvascular injury. METHODS: 
      Twenty-three patients with ketamine-induced cystitis (KC) and 16 control 
      volunteers were recruited. Bladder tissues were obtained from both groups by 
      cystoscopic biopsies. Phospho-S6 ribosomal protein (p-S6RP), an end product of 
      the mTOR pathway, was stained in the urinary bladder from both groups. 
      Endothelial cells of the urinary bladder (HBdMECs) were examined to investigate 
      the in vitro activation of the mTOR pathway and the co-expression of the 
      endothelial marker (cluster of differentiation 31 [CD31]) and the mesenchymal 
      marker (fibroblast-specific protein 1 [FSP-1]). RESULTS: Expression of p-S6RP 
      increased significantly after ketamine exposure, especially in the vesical 
      microvessels of KC patients. In HBdMECs treated with 100 microM Ketamine, 
      time-dependent activation of the mTOR pathway occurred, with significantly 
      increased levels of the phosphorylated forms of mTOR at 30 min and of S6RP and 
      p70S6 kinase (p70S6K) at 6 h. The increased level of p-S6RP returned to baseline 
      within 2 days after ketamine exposure. The co-expression of CD31 and FSP-1 
      implied that EndMT was present in HBdMECs at 7 days after ketamine treatment, 
      while TGF-beta1 facilitated significant up-regulation of FSP-1 at 1 day after 
      treatment. Furthermore, when the mTOR inhibitor rapamycin was administered with 
      ketamine to the HBdMECs, the expression of FSP-1 decreased significantly. 
      CONCLUSIONS: Ketamine induces activation of the mTOR pathway and subsequent 
      mesenchymal phenotypic expression (FSP1) in HBdMECs.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Lin, Chih-Chieh
AU  - Lin CC
AD  - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
AD  - Department of Urology, School of Medicine, National Yang-Ming University, Taipei, 
      Taiwan.
AD  - Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan.
FAU - Yang, An-Hang
AU  - Yang AH
AD  - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
AD  - Department of Pathology and Laboratory Medicine, Taipei Veterans General 
      Hospital, Taipei, Taiwan.
AD  - Department of Pathology, School of Medicine, National Yang-Ming University, 
      Taipei, Taiwan.
FAU - Lin, Alex Tong-Long
AU  - Lin AT
AD  - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
AD  - Department of Urology, School of Medicine, National Yang-Ming University, Taipei, 
      Taiwan.
AD  - Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20170221
PL  - United States
TA  - Neurourol Urodyn
JT  - Neurourology and urodynamics
JID - 8303326
RN  - 690G0D6V8H (Ketamine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Cystitis/chemically induced/*metabolism
MH  - Female
MH  - Humans
MH  - Ketamine/administration & dosage/*adverse effects
MH  - Male
MH  - Microvessels/drug effects/*metabolism
MH  - Middle Aged
MH  - Phosphorylation/drug effects
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Urinary Bladder/drug effects/*metabolism
MH  - Young Adult
OTO - NOTNLM
OT  - endothelial cell
OT  - endothelial mesenchymal transition
OT  - ketamine
OT  - mTOR pathway
OT  - microvascular injury
EDAT- 2017/02/22 06:00
MHDA- 2018/09/05 06:00
CRDT- 2017/02/22 06:00
PHST- 2016/11/04 00:00 [received]
PHST- 2016/12/16 00:00 [revised]
PHST- 2017/01/20 00:00 [accepted]
PHST- 2017/02/22 06:00 [pubmed]
PHST- 2018/09/05 06:00 [medline]
PHST- 2017/02/22 06:00 [entrez]
AID - 10.1002/nau.23234 [doi]
PST - ppublish
SO  - Neurourol Urodyn. 2017 Nov;36(8):1988-1995. doi: 10.1002/nau.23234. Epub 2017 Feb 
      21.