PMID- 19199859
OWN - NLM
STAT- MEDLINE
DCOM- 20101123
LR  - 20191210
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 22
IP  - 3
DP  - 2009 Mar 16
TI  - Protective effects of a synthesized butyrolactone derivative against 
      chloroquine-induced autophagic vesicle accumulation and the disturbance of 
      mitochondrial membrane potential and Na+,K+-ATPase activity in vascular 
      endothelial cells.
PG  - 471-5
LID - 10.1021/tx8002824 [doi]
AB  - We previously found a butyrolactone derivative, 3-benzyl-5-((2-nitrophenoxy) 
      methyl)-dihydrofuran-2(3H)-one (3BDO), could inhibit vascular endothelial cell 
      (VEC) apoptosis and senescence induced by a deprivation of serum and FGF-2. In 
      this study, we aimed to investigate its actions in VEC autophagy induced by 
      chloroquine (CQ). The measurement on the volume of acidic compartments (VAC) and 
      autophagy analysis by acridine orange (AO) staining and microtubule-associated 
      protein 1 light chain 3 (MAP1LC3) process revealed that 3BDO was an effective 
      inhibitor of autophagic vesicle accumulation (vacuolation) induced by CQ in VECs. 
      5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide 
      (JC-1) was used for mitochondrial membrane potential (MMP) measurement. The 
      results showed that CQ elevated MMP significantly and that 3BDO could 
      significantly inhibit CQ-induced MMP increase. Na+,K+-ATPase activity assay 
      showed that CQ inhibited this enzyme activity significantly and that 3BDO 
      attenuated the alteration of Na+,K+-ATPase activity caused by CQ. We concluded 
      that 3BDO was a promising inhibitor of CQ-induced accumulation of autophagic 
      vesicles in VECs and could weaken the alterations of MMP and Na+,K+-ATPase 
      activity induced by CQ. The data indicate that 3BDO will be a potential tool for 
      investigating the mechanism of autophagy.
FAU - Huang, Bin
AU  - Huang B
AD  - Institute of Developmental Biology, School of Life Science, Shandong University, 
      Jinan 250100, China.
FAU - Meng, Ning
AU  - Meng N
FAU - Zhao, Baoxiang
AU  - Zhao B
FAU - Zhao, Jing
AU  - Zhao J
FAU - Zhang, Yun
AU  - Zhang Y
FAU - Zhang, Shangli
AU  - Zhang S
FAU - Miao, Junying
AU  - Miao J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (3-benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3H)-one)
RN  - 886U3H6UFF (Chloroquine)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - OL659KIY4X (4-Butyrolactone)
SB  - IM
MH  - 4-Butyrolactone/*analogs & derivatives/chemistry/pharmacology
MH  - Autophagy/*drug effects
MH  - Cells, Cultured
MH  - Chloroquine/*toxicity
MH  - Cytoplasmic Vesicles/drug effects
MH  - Endothelial Cells/*drug effects/enzymology/physiology
MH  - Humans
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Sodium-Potassium-Exchanging ATPase/*metabolism
EDAT- 2009/02/10 09:00
MHDA- 2010/12/14 06:00
CRDT- 2009/02/10 09:00
PHST- 2009/02/10 09:00 [entrez]
PHST- 2009/02/10 09:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - 10.1021/tx8002824 [pii]
AID - 10.1021/tx8002824 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2009 Mar 16;22(3):471-5. doi: 10.1021/tx8002824.