Diethylnitrosamine- and partial hepatectomy-induced decrease in alpha 2u-globulin mRNA level in the rat liver.

K Matuoka; I Markus; A Wong; G J Smith

doi:10.1007/bf01372719

Home/Archive/PubMed

PubMed · 7687602

Diethylnitrosamine- and partial hepatectomy-induced decrease in alpha 2u-globulin mRNA level in the rat liver.

K Matuoka·I Markus·A Wong·G J Smith

View original source ↗Export metadata ↓

Abstract

Changes in gene expression in the rat liver were investigated by analyzing cDNA libraries for liver mRNAs from adult male rats injected with a chemical carcinogen diethylnitrosamine (DEN). Differential screening using normal and DEN-treated liver cDNAs as probes demonstrated that some of the mRNA species had noticeably lower abundance in the DEN-treated liver than in the untreated liver. Surprisingly, most of those clones were found to code for alpha 2u-globulin (A2uG), an abundant protein in the male rat liver. Further analysis by in situ hybridization revealed that the decrease in the A2uG mRNA level occurred in the area where liver cells were proliferating due to DEN treatment and/or partial hepatectomy (PH). The findings indicate coincidence of cell proliferation with a decrease in the A2uG gene expression in the adult male rat liver, implying that the A2uG-related change favors chemical carcinogen-induced cell growth.

Explore related subjects

Alpha-Globulins Animals Cell Division Cell Transformation, Neoplastic DNA Diethylnitrosamine Gene Expression Hepatectomy Liver Liver Neoplasms Male RNA, Messenger Rats Rats, Inbred F344 Journal Article Research Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

K Matuoka, I Markus, A Wong, G J Smith. 1993. Diethylnitrosamine- and partial hepatectomy-induced decrease in alpha 2u-globulin mRNA level in the rat liver.. https://doi.org/10.1007/bf01372719

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1998

Hepatic and extra-hepatic transcription of inter-alpha-inhibitor family genes under normal or acute inflammatory conditions in rat.

The expression and level of the mRNAs for the five genes that code for a set of plasma proteins collectively referred to as the inter-alpha-inhibitor family have been studied in rat under a normal condition or in the course of a turpentine-induced, systemic inflammation. In healthy rats, all five mRNAs [H1, H2, H3, H4, and alpha1-microglobulin/bikunin precursor (AMBP)] are expressed primarily in liver and two of them (H2 and H3) are found to a lower extent in brain. By in situ hybridization onto sections of a normal brain, the H3 mRNA has been precisely localized to the hypothalamus, amygdala, pontine area, optic tectum, and cerebellum. By reverse transcriptase-polymerase chain reaction of total RNAs obtained from a panel of organs, low amounts of one or more mRNA(s) could be detected in other locations (e.g., intestine and stomach). Furthermore, the extrahepatic expressions of several of these genes are up- or downregulated at 20 h after the start of a turpentine-induced inflammation. In liver, the contents of H3 and H4 mRNA are upregulated, whereas those of AMBP and H2 are downregulated during the acute phase. This is accounted for by changes in gene transcription, the kinetics of which is gene-specific. This behavior of H1, H2, H3, H4, and AMBP mRNAs in rat liver is in keeping with more limited analyses made at mRNA and/or protein levels in other species (human, pig) suffering from an acute inflammation. Therefore, the inflammation-associated regulation of these five genes that is conserved between species indicates that the inter-alpha-inhibitor family members are likely to be important partners of the acute phase response.

Alpha-Globulins↗

PubMed1998

The H4P heavy chain of inter-alpha-inhibitor family largely differs in the structure and synthesis of its prolin-rich region from rat to human.

The family of plasma proteins collectively referred to as Inter-alpha-Inhibitor (I alpha I) family is comprised of a set of multi-polypeptide molecules and a single-chain molecule designated I alpha IH4P. Although the 4 heavy chain precursors H1P to H4P that lead to these molecules are evolutionarily related, only H4P harbours a Pro-rich region (PRR) in its C-terminal third. A comparison of hepatic H4P cDNAs in human and rat has now unraveled an extensive variability of this PRR. Within the rat PRR, 6 repeats of a Gly-X-Pro motif participate in a collagen-like pattern that is absent in human. Within the human PRR, a domain that is absent in rat can be transcribed or deleted by alternative splicing which results in two variant forms of human H4P. In rat liver, the single mRNA is up-regulated by an acute, systemic inflammation whereas neither mRNA is up-regulated in human liver. Finally the shortest human mRNA is also transcribed in peripheral blood mononuclear cells where it is down-regulated by bacterial lipopolysaccharides. Therefore, in contrast to what is seen for the ITIH1 to -3 genes, the rat and human ITIH4 gene transcriptions and products thereof present marked differences, which suggests species-specific functions for I alpha IH4P.

Alpha-Globulins↗

PubMed1998

Cell swelling increased the alpha2-macroglobulin gene expression in cultured rat hepatocytes.

The effect of cell swelling on the expression of the alpha2-macroglobulin (alpha2M) gene was studied in hepatocytes in culture. Hypoosmolarity induced an increase (3-fold increase) in the level of alpha2M mRNA through a corresponding stimulation of the rate of transcription of the alpha2M gene. The addition of raffinose (100 mM) corrected the effect of hypoosmolarity at both mRNA and transcriptional level, demonstrating that cell swelling per se was responsible for the observed effect on the expression of the alpha2M gene. Moreover, the effect of cell swelling was additive to that of interleukin 6, a major mediator of the acute-phase response.

Alpha-Globulins↗