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Change in hepatic gene expression after shock/resuscitation.
T G Buchman1, D E Cabin, J M Porter
1Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Md.
Surgery
|August 1, 1989
Summary
Cells respond to stress by producing protective heat-shock proteins. This study investigated if liver cells in vivo similarly alter gene expression during cardiogenic shock, identifying metallothionein as a key stress-induced protein.
Area of Science:
- Cellular biology
- Molecular biology
- Physiology
Background:
- Isolated cells (prokaryotic and eukaryotic) synthesize heat-shock proteins in response to stress for homeostasis.
- Circulatory shock presents a complex stress to parenchymal cells in vivo.
Purpose of the Study:
- To determine if parenchymal cells in vivo exhibit a similar stress response during cardiogenic shock.
- To identify specific genes and proteins upregulated in response to shock/resuscitation.
Main Methods:
- Liver biopsy specimens were collected from a swine model of cardiogenic shock before and after resuscitation.
- Complementary DNA libraries were constructed from post-shock/resuscitation messenger RNA.
- Differential gene expression was screened, with positive clones confirmed by Northern blot analysis.
Main Results:
- Six out of 4000 screened clones showed confirmed induction after shock/resuscitation.
- Nucleotide sequences of two clones were determined.
- One identified gene was metallothionein, indicating its upregulation during shock.
Conclusions:
- Parenchymal cells in vivo demonstrate altered gene expression in response to cardiogenic shock.
- Metallothionein is identified as a stress-induced protein in the liver during circulatory shock.
- This response is analogous to the heat-shock protein response observed in isolated cells.