The hepatocyte protein synthesis defect induced by galactosamine involves hypomethylation of ribosomal RNA

Gary Clawson, Julie Sesno, Kathy Milam, Yan‐Fel ‐F Wang, Caroline Gabriel

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

D‐galactosamine produces an early defect in protein synthesis, independent of its effects on RNA synthcsis. Here we show that the defect in protein synthesis is inherent in purified ribosomal subunits in vitro. Furthere, galactosamine treatment is associated with an 85% decrease in methylation of ribosomal RNA, involving all sites (2′‐0‐ronpse and base positions), intact ribosomes from galactosamine‐treated animals can be methylated to a greater extent than control ribosomes and in vitro methylation restores their funtional capacity. Statistical analyes of these data, along with those with a number of other hepatotoxins, reveal a correlation coefficent of r = 0.95 (p < 0.003) between protein synthetic capacity and ribosomal RNA methylaiton, and linear regression accounts for more than 90% of the observed variation. In contrast, no relationship was found between nucleolar RNA methylation and protein synthetic capacity. A relationship of borderline statistical significance was found between messenger RNA methylaiton and protein synthetic capacity, but it does not appear consistent with results obtained after CCI 4 intoxication. These results lend strong support ot the notion that methylation status of ribosomal RNA is an important control for protein synthesis in quiscent hepatocytes and that net hypomethylation is a common responses to such divergent hepatotoxins as CCI 4 , ethionine and D‐galactosamine. (HEPATOLOGY 1990;11:428–434.)

Original languageEnglish (US)
Pages (from-to)428-434
Number of pages7
JournalHepatology
Volume11
Issue number3
DOIs
StatePublished - Jan 1 1990

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Galactosamine
Ribosomal RNA
Hepatocytes
Methylation
Proteins
Ribosomes
RNA
Ethionine
Ribosome Subunits
Linear Models
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Clawson, Gary ; Sesno, Julie ; Milam, Kathy ; Wang, Yan‐Fel ‐F ; Gabriel, Caroline. / The hepatocyte protein synthesis defect induced by galactosamine involves hypomethylation of ribosomal RNA. In: Hepatology. 1990 ; Vol. 11, No. 3. pp. 428-434.
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abstract = "D‐galactosamine produces an early defect in protein synthesis, independent of its effects on RNA synthcsis. Here we show that the defect in protein synthesis is inherent in purified ribosomal subunits in vitro. Furthere, galactosamine treatment is associated with an 85{\%} decrease in methylation of ribosomal RNA, involving all sites (2′‐0‐ronpse and base positions), intact ribosomes from galactosamine‐treated animals can be methylated to a greater extent than control ribosomes and in vitro methylation restores their funtional capacity. Statistical analyes of these data, along with those with a number of other hepatotoxins, reveal a correlation coefficent of r = 0.95 (p < 0.003) between protein synthetic capacity and ribosomal RNA methylaiton, and linear regression accounts for more than 90{\%} of the observed variation. In contrast, no relationship was found between nucleolar RNA methylation and protein synthetic capacity. A relationship of borderline statistical significance was found between messenger RNA methylaiton and protein synthetic capacity, but it does not appear consistent with results obtained after CCI 4 intoxication. These results lend strong support ot the notion that methylation status of ribosomal RNA is an important control for protein synthesis in quiscent hepatocytes and that net hypomethylation is a common responses to such divergent hepatotoxins as CCI 4 , ethionine and D‐galactosamine. (HEPATOLOGY 1990;11:428–434.)",
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The hepatocyte protein synthesis defect induced by galactosamine involves hypomethylation of ribosomal RNA. / Clawson, Gary; Sesno, Julie; Milam, Kathy; Wang, Yan‐Fel ‐F; Gabriel, Caroline.

In: Hepatology, Vol. 11, No. 3, 01.01.1990, p. 428-434.

Research output: Contribution to journalArticle

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