PMID- 11045937
OWN - NLM
STAT- MEDLINE
DCOM- 20001228
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 279
IP  - 5
DP  - 2000 Nov
TI  - Endotoxin infusion in rats induces apoptotic and survival pathways in hearts.
PG  - H2053-61
AB  - Inflammatory mediators of sepsis induce apoptosis in many cell lines. We tested 
      the hypothesis that lipopolysaccharide (LPS) injection in vivo results in 
      induction of early apoptotic and survival pathways as well as evidence of 
      late-stage apoptosis in the heart. Hearts were collected from control rats and at 
      6, 12, and 24 h after LPS injection (4 mg/kg). Activation of an apoptotic pathway 
      was identified by a 1,000-fold increase in caspase-3 activity at 24 h (P < 0.05). 
      Confirmation of these results occurred when terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) staining identified 
      myocardial cells undergoing DNA fragmentation with significant levels at 24 h 
      post-LPS injection. LPS also caused early proapoptotic mRNA (Bax) to increase 
      (16% at 24 h, P < 0.05), whereas the Bax protein initially decreased (35% at 6 h, 
      P < 0.05) and then returned to baseline values by 24 h. Six hours after LPS 
      injection, Bcl-2 (early prosurvival) mRNA levels increased, whereas its protein 
      levels decreased (70%, P < 0.05) and then returned to baseline levels by 24 h. 
      Mitochondrial cytochrome c levels decreased, suggestive of mitochondrial 
      involvement. Thus involvement of proapoptotic and prosurvival pathways in the 
      heart occurs during a septic inflammatory response.
FAU - McDonald, T E
AU  - McDonald TE
AD  - University of British Columbia Pulmonary Research Laboratory, St. Paul's 
      Hospital, Vancouver, British Columbia, Canada.
FAU - Grinman, M N
AU  - Grinman MN
FAU - Carthy, C M
AU  - Carthy CM
FAU - Walley, K R
AU  - Walley KR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Bax protein, rat)
RN  - 0 (Endotoxins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Survival/physiology
MH  - DNA Fragmentation
MH  - Disease Models, Animal
MH  - Endotoxins
MH  - Lipopolysaccharides
MH  - Male
MH  - Myocardium/*metabolism/pathology
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sepsis/chemically induced/*metabolism
MH  - bcl-2-Associated X Protein
EDAT- 2000/10/25 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/25 11:00
PHST- 2000/10/25 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/25 11:00 [entrez]
AID - 10.1152/ajpheart.2000.279.5.H2053 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2053-61. doi: 
      10.1152/ajpheart.2000.279.5.H2053.