PMID- 25392259
OWN - NLM
STAT- MEDLINE
DCOM- 20150717
LR  - 20181113
IS  - 1877-8755 (Electronic)
IS  - 1138-7548 (Linking)
VI  - 70
IP  - 4
DP  - 2014 Dec
TI  - Tumor necrosis factor-alpha-induced microvascular endothelial cell hyperpermeability: 
      role of intrinsic apoptotic signaling.
PG  - 971-80
LID - 10.1007/s13105-014-0366-8 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha), a pro-apoptotic cytokine, is involved in 
      vascular hyperpermeability, tissue edema, and inflammation. We hypothesized that 
      TNF-alpha induces microvascular hyperpermeability through the mitochondria-mediated 
      intrinsic apoptotic signaling pathway. Rat lung microvascular endothelial cells 
      grown on Transwell inserts, chamber slides, or dishes were treated with 
      recombinant TNF-alpha (10 ng/ml) in the presence or absence of a caspase-3 inhibitor, 
      Z-DEVD-FMK (100 muM). Fluorescein isothiocyanate (FITC)-albumin (5 mg/ml) was used 
      as a marker of monolayer permeability. Mitochondrial reactive oxygen species 
      (ROS) was determined using dihydrorhodamine 123 and mitochondrial transmembrane 
      potential using JC-1. The adherens junction integrity and actin cytoskeletal 
      organization were studied using beta-catenin immunofluorescence and rhodamine 
      phalloidin, respectively. Caspase-3 activity was measured fluorometrically. The 
      pretreatment with Z-DEVD-FMK (100 muM) attenuated TNF-alpha-induced (10 ng/ml) 
      disruption of the adherens junctions, actin stress fiber formation, increased 
      caspase-3 activity, and monolayer hyperpermeability (p < 0.05). TNF-alpha (10 ng/ml) 
      treatment resulted in increased mitochondrial ROS formation and decreased 
      mitochondrial transmembrane potential. Intrinsic apoptotic signaling-mediated 
      caspase-3 activation plays an important role in regulating TNF-alpha-induced 
      endothelial cell hyperpermeability.
FAU - Sawant, Devendra A
AU  - Sawant DA
AD  - Department of Surgery, Morehouse School of Medicine, 720 Westview Drive SW, 
      Atlanta, GA, 30310, USA.
FAU - Wilson, Rickesha L
AU  - Wilson RL
FAU - Tharakan, Binu
AU  - Tharakan B
FAU - Stagg, Hayden W
AU  - Stagg HW
FAU - Hunter, Felicia A
AU  - Hunter FA
FAU - Childs, Ed W
AU  - Childs EW
LA  - eng
GR  - 1K01HL07815-01A1/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141114
PL  - Spain
TA  - J Physiol Biochem
JT  - Journal of physiology and biochemistry
JID - 9812509
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Adherens Junctions/metabolism
MH  - Animals
MH  - *Apoptosis
MH  - Capillary Permeability
MH  - Caspase 3/metabolism
MH  - Cell Membrane Permeability
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*cytology
MH  - Membrane Potential, Mitochondrial
MH  - Microvessels/*cytology
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 2014/11/14 06:00
MHDA- 2015/07/18 06:00
CRDT- 2014/11/14 06:00
PHST- 2013/11/11 00:00 [received]
PHST- 2014/10/23 00:00 [accepted]
PHST- 2014/11/14 06:00 [entrez]
PHST- 2014/11/14 06:00 [pubmed]
PHST- 2015/07/18 06:00 [medline]
AID - 10.1007/s13105-014-0366-8 [doi]
PST - ppublish
SO  - J Physiol Biochem. 2014 Dec;70(4):971-80. doi: 10.1007/s13105-014-0366-8. Epub 
      2014 Nov 14.