Expression, Purification, Crystallization and Preliminary X-ray Analysis of the Augmenter of Liver Regeneration (original) (raw)

A fresh look at augmenter of liver regeneration in rats

…, 1999

Augmenter of liver regeneration (ALR) is a hepatottophic protein originally identified by bioassay in regenetatingrat and canine livers following partial hepatectomy and in the hyperplastic livers of weanling rats, but not in testing adult livers. The ALR gene and gene product w~re ~ubseque:r1tly described, but little is known about the cellular/subcellular sites of ALR synthesis in the liver, or about the release and dissemination of the peptide. To obtain this information in rats, .we raised antibodies in rabbits against rat ALR for development of an enzyme-linked immunosorbent assay (ELISA). ALR concentrations were then determined in intact livers of unaltered weanling and adult rats; in regenerating residual liver after partial hepatectomy; in cultured hepatocytes and nonparenchymal cells (NPCs); and in cultnremedium and serum. ALR in the various liver cells Was localized with immunohistochemistry. In addition, hepatic ALRand ALR mRNA were as'sayed with Western blotting and reverse~ transcriptase polymera~e chain reacHon (RT-peR), respectively. The hepatocyte was the predominant liver cell in which ALR waS. synthesized and stored;' t.h,e cultured hepatocytes s~creted ALR into the medium in a timedependent fashiori.• Contrary to previous belid, the ALR peptide and ALR niRNA were present in comparable concentrations in the hepatocytes of both weanling and reSting adult livers, as well' as in cultured hepatocytes. A further unexpected finding was that hepatic ALR levels decreas~d for 12 hours after 70% hepatectomy in adult rats and then rose with no corresponding change inmRNA transcripts. In the meantime, circulating (serum) ALR levels increased up to 12 hours and declined thereafter. Thus, ALR appears to be constitutively expressed in hepatocytes in an inactive form, and released from the cells in an active form by unknown means in response to partial hepatectomy and under other circumstances of liver maturation (as in weanling ratS) or regeneration.

Augmenter of liver regeneration: Its place in the universe of hepatic growth factors

Hepatology, 1994

As every school child knows, chameleons can regenerate a lost tail. Indeed, regrowth of appendages is a not uncommon phenomenon among other lower animals. In mammals, however, regenerative capacity is much more restricted. The special regenerative capability of the mammalian liver has been recognized over millennia, as epitomized by the ancient legend of Prometheus. The explanation for liver regeneration has been of interest to investigators for more than a century. With the convergence in our laboratory of two lines of inquiry more than a third of a century ago, this quest for understanding received a major stimulus.

Analysis of the structure and expression of the augmenter of liver regeneration (ALR) gene

1996

Background: The gene encoding the hepatotrophic factor Augmenter of Liver Regeneration (ALR) has recently been cloned in the rat. The availability of the mouse form of ALR would allow the analysis of the role of this factor in the physiology of liver and other organs, while the identification of the human homolog would allow the transfer of the great wealth of information that has been generated in animal models to clinically oriented pilot trials, and eventually the therapeutic application of this information. Materials and Methods: Standard molecular biology approaches have been used to determine the genomic structure of the ALR gene in the mouse, and to characterize the ALR transcript and its protein product. The human ALR cDNA was also isolated and the amino acid sequence of the human gene product deduced. The mapping of mouse and human ALR genes on mouse and human chromosomes was then completed.