PMID- 18430368
OWN - NLM
STAT- MEDLINE
DCOM- 20090507
LR  - 20131121
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Linking)
VI  - 29
IP  - 5
DP  - 2008 May
TI  - Chronic activation of neutral ceramidase protects beta-cells against 
      cytokine-induced apoptosis.
PG  - 593-9
LID - 10.1111/j.1745-7254.2008.00781.x [doi]
AB  - AIM: To investigate the activity and expression of neutral ceramidase (N-CDase) 
      in the insulin-secreting cell line INS-1 and its role in the cellular response to 
      cytokines. METHODS: HPLC, Western blotting, and quantitative real-time PCR were 
      performed to detect the activity and expression of N-CDase in INS-1 cells treated 
      with a cytokine mixture (5 ng/mL interleukin-1beta, 10 ng/mL TNF-alpha, and 50 
      ng/mL interferon-gamma). The expression and activity of N-CDase in the INS-1 
      cells were specifically inhibited using N-CDase-siRNA transfection. Annexin 
      V-fluorescein- isothiocyanate/propidium iodide flow cytometry was used to assess 
      apoptosis in the INS-1 cells. RESULTS: The INS-1 cells exhibited some basal 
      N-CDase activity, and cytokines induced a time-dependent delay in the activation 
      of NCDase. As a result, the activation of N-CDase was first detectable at 8 h 
      after stimulation. It peaked at 16 h and remained elevated at 24 h. Cytokines 
      also upregulated the mRNA and protein expression of N-CDase in the INS-1 cells. 
      Furthermore, when N-CDase activity was inhibited by RNA interference, 
      cytokine-induced apoptosis in the INS-1 cells was markedly increased. CONCLUSION: 
      The N-CDase pathway is active in INS-1 cells, and the chronic activation of 
      N-CDase is involved in the pathological response of beta-cells to cytokines, 
      potentially providing protection against cytokine toxicity.
FAU - Zhu, Qun
AU  - Zhu Q
AD  - Department of Endocrinology, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing 210029, China.
FAU - Jin, Jun-Fei
AU  - Jin JF
FAU - Shan, Xiao-Hong
AU  - Shan XH
FAU - Liu, Cui-Ping
AU  - Liu CP
FAU - Mao, Xiao-Dong
AU  - Mao XD
FAU - Xu, Kuan-Feng
AU  - Xu KF
FAU - Liu, Chao
AU  - Liu C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Annexin A5)
RN  - 0 (Coloring Agents)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Cytokines)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 36015-30-2 (Propidium)
RN  - EC 3.5.1.23 (Neutral Ceramidase)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Animals
MH  - Annexin A5/metabolism
MH  - Apoptosis/*drug effects
MH  - Cell Line
MH  - Coloring Agents/metabolism
MH  - Culture Media, Serum-Free
MH  - Cytokines/genetics/*toxicity
MH  - Enzyme Activation/drug effects
MH  - Fluorescein-5-isothiocyanate/metabolism
MH  - Fluorescent Dyes/metabolism
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Insulin-Secreting Cells/*metabolism
MH  - Necrosis/metabolism
MH  - Neutral Ceramidase/*metabolism
MH  - Propidium/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Recombinant Proteins/toxicity
MH  - Time Factors
EDAT- 2008/04/24 09:00
MHDA- 2009/05/08 09:00
CRDT- 2008/04/24 09:00
PHST- 2008/04/24 09:00 [pubmed]
PHST- 2009/05/08 09:00 [medline]
PHST- 2008/04/24 09:00 [entrez]
AID - 10.1111/j.1745-7254.2008.00781.x [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2008 May;29(5):593-9. doi: 10.1111/j.1745-7254.2008.00781.x.