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Temperature-sensitive mRNA degradation is an early event in hepatocyte de-differentiation.

Publication ,  Journal Article
Wang, XJ; Hodgkinson, CP; Wright, MC; Paine, AJ
Published in: Biochem J
December 15, 1997

The isolation and culture of metabolically active hepatocytes by proteolytic digestion of the extracellular matrix of the liver results in the transcriptional silencing of liver-specific genes encoding cytochromes P-450 (CYP) and albumin together with an induction of cellular RNase activity. The levels of albumin mRNA are maintained in cultured hepatocytes at similar levels to that present in the intact liver for at least 24 h, whereas the major constitutively expressed CYP2C11 mRNA is rapidly degraded. Hepatocytes heat-shocked at 40 degrees C during the isolation procedure (which results in an induction of heat-shock protein mRNA species) blocks the increase in RNase activity and abrogates the loss of CYP2C11 mRNA for at least 4 h. Cycloheximide-dependent inhibition of protein synthesis blocks the temperature-dependent induction of heat-shock proteins without affecting the protection afforded to CYP2C11 mRNA, indicating that CYP2C11 mRNA levels are not directly dependent on heat-shock protein induction and suggesting that the induction of RNase activity might be responsible for the specific loss of CYP2C11 mRNA in hepatocytes isolated at 37 degrees C. Differential rates of degradation of CYP2C11 transcribed in vitro and of albumin mRNA are observed in the presence of cellular extracts from cultured hepatocytes isolated at 37 degrees C (which have maximally induced levels of cellular RNase activity) but not in comparable extracts from cultured hepatocytes isolated at 40 degrees C, supporting the hypothesis that an RNase activity is induced in culture that specifically degrades CYP2C11 mRNA but not albumin mRNA. These results suggest that an early event in hepatocyte de-differentiation involves the induction of RNase activity in addition to transcriptional silencing of liver-specific genes and that the induced RNase activity demonstrates specificity within liver-specific gene products.

Duke Scholars

Published In

Biochem J

DOI

ISSN

0264-6021

Publication Date

December 15, 1997

Volume

328 ( Pt 3)

Issue

Pt 3

Start / End Page

937 / 944

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Temperature
  • Ribonucleases
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Microsomes, Liver
  • Male
  • Liver
  • Heat-Shock Proteins
 

Citation

APA
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ICMJE
MLA
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Wang, X. J., Hodgkinson, C. P., Wright, M. C., & Paine, A. J. (1997). Temperature-sensitive mRNA degradation is an early event in hepatocyte de-differentiation. Biochem J, 328 ( Pt 3)(Pt 3), 937–944. https://doi.org/10.1042/bj3280937
Wang, X. J., C. P. Hodgkinson, M. C. Wright, and A. J. Paine. “Temperature-sensitive mRNA degradation is an early event in hepatocyte de-differentiation.Biochem J 328 ( Pt 3), no. Pt 3 (December 15, 1997): 937–44. https://doi.org/10.1042/bj3280937.
Wang XJ, Hodgkinson CP, Wright MC, Paine AJ. Temperature-sensitive mRNA degradation is an early event in hepatocyte de-differentiation. Biochem J. 1997 Dec 15;328 ( Pt 3)(Pt 3):937–44.
Wang, X. J., et al. “Temperature-sensitive mRNA degradation is an early event in hepatocyte de-differentiation.Biochem J, vol. 328 ( Pt 3), no. Pt 3, Dec. 1997, pp. 937–44. Pubmed, doi:10.1042/bj3280937.
Wang XJ, Hodgkinson CP, Wright MC, Paine AJ. Temperature-sensitive mRNA degradation is an early event in hepatocyte de-differentiation. Biochem J. 1997 Dec 15;328 ( Pt 3)(Pt 3):937–944.
Journal cover image

Published In

Biochem J

DOI

ISSN

0264-6021

Publication Date

December 15, 1997

Volume

328 ( Pt 3)

Issue

Pt 3

Start / End Page

937 / 944

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Temperature
  • Ribonucleases
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Microsomes, Liver
  • Male
  • Liver
  • Heat-Shock Proteins