Limits...
Phenotypic reversion in analbuminemic rats due to an altered splicing mechanism.

Esumi H, Sugimura T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2007)

Bottom Line: Surprisingly, many immunoreactive hepatocytes were observed after hepatocarcinogen treatment sometimes in large clusters.Albumin transcripts in analbuminemic rat liver after treatment with carcinogen, showed an altered pattern of exon-skipping.The altered albumin molecules thus synthesized accumulated in cellular organelles.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan .

ABSTRACT
Serum albumin is regarded as an important and indispensable protein, but analbuminemic rats established by Sumi Nagase in 1977 seems to exhibit few symptoms in spite of an almost total lack of albumin in the serum. The albumin gene of analbuminemic rats was found to have a seven-base-pair deletion in an intron, close to exon-intron junction, resulting in the formation of non-functional mRNA in hepatocytes. Immunostaining for albumin was negative in young analbuminemic rat hepatocytes, but a significant number of immunoreactive hepatocytes were observed in aged rats. The incidence of immunoreactive hepatocytes increased with aging. Surprisingly, many immunoreactive hepatocytes were observed after hepatocarcinogen treatment sometimes in large clusters. Albumin transcripts in analbuminemic rat liver after treatment with carcinogen, showed an altered pattern of exon-skipping. The altered albumin molecules thus synthesized accumulated in cellular organelles. Analbuminemic rats exhibited a high sensitivity in various organs to different types of carcinogens. Further challenges remain regarding the biology of analbuminemic rats.

No MeSH data available.


Change in anti-albumin antibody-reacting protein concentrations in serum of analbuminemic rats with age and in response to a carcinogen.Carcinogen treatment started at 4 weeks after birth. Serum anti-albumin was measured by a single radial immunodiffusion method using a polyclonal antiserum against rat serum albumin. Open circles indicate anti-albumin antibody-reacting protein concentrations in the serum of analbuminemic rats without carcinogen treatment and solid circles are for rats fed on 0.06% 3’-methyl-4-dimethlaminoazobenzene in basal CE-2 pellet diet (adopted with permission from Biochem. Biophys. Res. Commun. 106, 863–870 (1982)).22)
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3756734&req=5

f4-83_101: Change in anti-albumin antibody-reacting protein concentrations in serum of analbuminemic rats with age and in response to a carcinogen.Carcinogen treatment started at 4 weeks after birth. Serum anti-albumin was measured by a single radial immunodiffusion method using a polyclonal antiserum against rat serum albumin. Open circles indicate anti-albumin antibody-reacting protein concentrations in the serum of analbuminemic rats without carcinogen treatment and solid circles are for rats fed on 0.06% 3’-methyl-4-dimethlaminoazobenzene in basal CE-2 pellet diet (adopted with permission from Biochem. Biophys. Res. Commun. 106, 863–870 (1982)).22)

Mentions: When formalin-fixed sections of the livers of analbuminemic rats were subjected to immunostaining using anti-albumin antibody, the entire liver was found to lack staining. However, mysteriously the presence of cells immunoreactive to anti-albumin antibody (immunoreactive cells) was noted at a rate of one per several microscopic fields under 100-times magnification. Interestingly, very minute amounts of a serum protein reactive with anti-albumin antibody were also present in alb−/− rats, and increased with age, as shown with open circles in Fig. 4. Indeed, clusters of several cells that were immunoreactive with the anti-albumin antibody were readily detectable in aged alb−/− rats, and their incidence increased over time. We suspected phenotypic reversion of albumin-negative cells to albumin-positive cells were not able to prove this at the time. Consistent with this idea, serum concentration of protein reactive with anti-albumin antibody increased in carcinogen-treated rats more significantly than in untreated rats, but the effect of carcinogen treatment on increment was about 2 fold over that in untreated rats (Fig. 4).7)


Phenotypic reversion in analbuminemic rats due to an altered splicing mechanism.

Esumi H, Sugimura T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2007)

Change in anti-albumin antibody-reacting protein concentrations in serum of analbuminemic rats with age and in response to a carcinogen.Carcinogen treatment started at 4 weeks after birth. Serum anti-albumin was measured by a single radial immunodiffusion method using a polyclonal antiserum against rat serum albumin. Open circles indicate anti-albumin antibody-reacting protein concentrations in the serum of analbuminemic rats without carcinogen treatment and solid circles are for rats fed on 0.06% 3’-methyl-4-dimethlaminoazobenzene in basal CE-2 pellet diet (adopted with permission from Biochem. Biophys. Res. Commun. 106, 863–870 (1982)).22)
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756734&req=5

f4-83_101: Change in anti-albumin antibody-reacting protein concentrations in serum of analbuminemic rats with age and in response to a carcinogen.Carcinogen treatment started at 4 weeks after birth. Serum anti-albumin was measured by a single radial immunodiffusion method using a polyclonal antiserum against rat serum albumin. Open circles indicate anti-albumin antibody-reacting protein concentrations in the serum of analbuminemic rats without carcinogen treatment and solid circles are for rats fed on 0.06% 3’-methyl-4-dimethlaminoazobenzene in basal CE-2 pellet diet (adopted with permission from Biochem. Biophys. Res. Commun. 106, 863–870 (1982)).22)
Mentions: When formalin-fixed sections of the livers of analbuminemic rats were subjected to immunostaining using anti-albumin antibody, the entire liver was found to lack staining. However, mysteriously the presence of cells immunoreactive to anti-albumin antibody (immunoreactive cells) was noted at a rate of one per several microscopic fields under 100-times magnification. Interestingly, very minute amounts of a serum protein reactive with anti-albumin antibody were also present in alb−/− rats, and increased with age, as shown with open circles in Fig. 4. Indeed, clusters of several cells that were immunoreactive with the anti-albumin antibody were readily detectable in aged alb−/− rats, and their incidence increased over time. We suspected phenotypic reversion of albumin-negative cells to albumin-positive cells were not able to prove this at the time. Consistent with this idea, serum concentration of protein reactive with anti-albumin antibody increased in carcinogen-treated rats more significantly than in untreated rats, but the effect of carcinogen treatment on increment was about 2 fold over that in untreated rats (Fig. 4).7)

Bottom Line: Surprisingly, many immunoreactive hepatocytes were observed after hepatocarcinogen treatment sometimes in large clusters.Albumin transcripts in analbuminemic rat liver after treatment with carcinogen, showed an altered pattern of exon-skipping.The altered albumin molecules thus synthesized accumulated in cellular organelles.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan .

ABSTRACT
Serum albumin is regarded as an important and indispensable protein, but analbuminemic rats established by Sumi Nagase in 1977 seems to exhibit few symptoms in spite of an almost total lack of albumin in the serum. The albumin gene of analbuminemic rats was found to have a seven-base-pair deletion in an intron, close to exon-intron junction, resulting in the formation of non-functional mRNA in hepatocytes. Immunostaining for albumin was negative in young analbuminemic rat hepatocytes, but a significant number of immunoreactive hepatocytes were observed in aged rats. The incidence of immunoreactive hepatocytes increased with aging. Surprisingly, many immunoreactive hepatocytes were observed after hepatocarcinogen treatment sometimes in large clusters. Albumin transcripts in analbuminemic rat liver after treatment with carcinogen, showed an altered pattern of exon-skipping. The altered albumin molecules thus synthesized accumulated in cellular organelles. Analbuminemic rats exhibited a high sensitivity in various organs to different types of carcinogens. Further challenges remain regarding the biology of analbuminemic rats.

No MeSH data available.