PMID- 7728586
OWN - NLM
STAT- MEDLINE
DCOM- 19950601
LR  - 20190913
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 2
IP  - 2
DP  - 1994 Aug
TI  - Thiol reducing agents modulate induced apoptosis in porcine endothelial cells.
PG  - 79-83
AB  - When cultured porcine endothelial cells are exposed first to endotoxin 
      (lipopolysaccharide (LPS)) followed by standard inducers of the heat shock 
      response in vitro (heat or sodium arsenite), these cells aberrantly execute 
      programmed cell death. This cell death is dependent upon two distinct events: the 
      LPS-priming step and the heat shock-induced activation step. Prior work 
      demonstrated that the LPS-priming step could be blocked by the prior application 
      of cell-permeable hydroxyl radical scavengers, suggesting a role for this 
      reactive oxygen species as an important intracellular signal mediating the first 
      step. In these present experiments, we evaluated the potential role of 
      reduction-oxidation mechanisms in the heat shock activation step. The thiol 
      reducing agents reduced glutathione (GSH), n-acetylcysteine (NAC), and 
      dithiothreitol (DTT) were evaluated for their ability to block programmed cell 
      death in LPS-primed porcine aortic endothelial cells. Both DTT and NAC, agents 
      that augment intracellular reduced glutathione levels, were protective against 
      cell death when applied prior to heat shock induction with sodium arsenite (As) 
      in endothelial cells treated previously with LPS. The less cell permeable agent 
      GSH was not protective. Delayed application of DTT or NAC could block progression 
      to cell death for up to 1.5 h after initiation of the heat shock response with 
      As. These data show that heat shock-induced programmed cell death in LPS-primed 
      endothelial cells can be arrested, at least in its early stages, by agents that 
      augment or stabilize the reducing potential of the cell.(ABSTRACT TRUNCATED AT 
      250 WORDS)
FAU - Abello, P A
AU  - Abello PA
AD  - Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland 21287-2244, USA.
FAU - Fidler, S A
AU  - Fidler SA
FAU - Buchman, T G
AU  - Buchman TG
LA  - eng
GR  - GM 00581/GM/NIGMS NIH HHS/United States
GR  - GM 48095/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - GAN16C9B8O (Glutathione)
RN  - T8ID5YZU6Y (Dithiothreitol)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*pharmacology
MH  - Animals
MH  - Aorta
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Dithiothreitol/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/cytology/*drug effects/physiology
MH  - Female
MH  - Free Radical Scavengers/pharmacology
MH  - Glutathione/metabolism
MH  - Heat-Shock Proteins/biosynthesis
MH  - Kinetics
MH  - Lipopolysaccharides/pharmacology
MH  - Swine
EDAT- 1994/08/01 00:00
MHDA- 1994/08/01 00:01
CRDT- 1994/08/01 00:00
PHST- 1994/08/01 00:00 [pubmed]
PHST- 1994/08/01 00:01 [medline]
PHST- 1994/08/01 00:00 [entrez]
AID - 10.1097/00024382-199408000-00001 [doi]
PST - ppublish
SO  - Shock. 1994 Aug;2(2):79-83. doi: 10.1097/00024382-199408000-00001.