Phenobarbitone – induced liver response in wild type and in p53 deficient mice

Gould, Sarah; Sidaway, James E.; Sansom, Nigel; Betton, Graham; Orton, Terry C.

doi:10.1016/s0378-4274(01)00349-6

Cited by 4 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed hypertrophy of hepatocytes around the central vein (Fig. 2) as previously noticed after long term administration of phenobarbital (Anon, 2000;Berman et al, 1983;Gould et al, 2001). Mild (grade 2) to moderate (grade 3) centrilobular hypertrophy was present in all animals.…”

Section: Immunohistochemical Analysis Of Treated Rat Liversupporting

confidence: 81%

“…Therefore, phenobarbital is able to amplify cells that have been initiated in response to a carcinogen leading to tumors (Peraino et al, 1971;Peraino et al, 1973). In contrast, phenobarbital alone does not cause liver tumors in rats (Anon, 2000;Gould et al, 2001). In the present study, rats were fed CPA for two consecutive days and injected with retroviral vectors containing a h-galactosidase gene to specifically label the population of hepatocytes stimulated by the mitogenic activity of CPA.…”

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

Long term phenobarbital administration does not promote the multiplication of hepatocytes replicating after single cyproterone acetate administration

Pichard

Ferry

2005

Life Sciences

View full text Add to dashboard Cite

Section: Immunohistochemical Analysis Of Treated Rat Liversupporting

confidence: 81%

Section: Introductionmentioning

confidence: 91%

Long term phenobarbital administration does not promote the multiplication of hepatocytes replicating after single cyproterone acetate administration

Pichard

Ferry

2005

Life Sciences

View full text Add to dashboard Cite

“…In pathological situations, animal cells may proliferate without a need for compensation for cell loss, resulting in hyperplasia, which is a pathological phraseology for the existence of extra (redundant) cells, usually with enlargement of the affected organ as a sequel. For example, some chemicals such as phenobarbital [ 62 , 63 ] or lead nitrate [ 64 ] can induce proliferation of hepatocytes, resulting in liver enlargement [ 41 ]. Aberrant expression or mutation of some genes, usually oncogenes, may also coerce the affected cells to replicate directly [ 55 ].…”

Section: Introductionmentioning

confidence: 99%

There are only four basic modes of cell death, although there are many ad-hoc variants adapted to different situations

et al. 2018

View full text Add to dashboard Cite

There have been enough cell death modes delineated in the biomedical literature to befuddle all cell death researchers. Mulling over cell death from the viewpoints of the host tissue or organ and of the host animal, we construe that there should be only two physiological cell death modes, i.e. apoptosis and senescent death (SD), as well as two pathological modes, i.e. necrosis and stress-induced cell death (SICD). Other death modes described in the literature are ad-hoc variants or coalescences of some of these four basic ones in different physiological or pathological situations. SD, SICD and necrosis kill useful cells and will thus trigger regeneration, wound healing and probably also scar formation. SICD and necrosis will likely instigate inflammation as well. Apoptosis occurs as a mechanism to purge no-longer useful cells from a tissue via phagocytosis by cells with phagocytic ability that are collectively tagged by us as scavengers, including macrophages; therefore apoptosis is not followed by regeneration and inflammation. The answer for the question of “who dies” clearly differentiates apoptosis from SD, SICD and necrosis, despite other similarities and disparities among the four demise modes. Apoptosis cannot occur in cell lines in vitro, because cell lines are immortalized by reprogramming the death program of the parental cells, because in culture there lack scavengers and complex communications among different cell types, and because culture condition is a stress to the cells. Several issues of cell death that remain enigmatic to us are also described for peers to deliberate and debate.

show abstract

“…Previous studies reported that no obvious abnormal liver histology was found with short-term deletion of p53; in contrast, deletion of p53 induces liver cancer after 10-12 months in mouse model(53). Several studies showed that loss of p53 did not significantly accelerate phenobarbitone or diethylnitrosamine-induced hepatocellular carcinoma(54-56). Thus, our finding suggests an important connection between p53 and Hippo pathway, two key pathways for maintaining quiescence of hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

RNAi-nanoparticulate manipulation of gene expression as a new functional genomics tool in the liver

Yin

Bogorad

Barnes

et al. 2016

Journal of Hepatology

View full text Add to dashboard Cite

Background and aims The Hippo pathway controls organ size through a negative regulation of the transcription co-activator Yap1. The overexpression of hyperactive mutant Yap1 or deletion of key components in the Hippo pathway leads to increased organ size in different species. Analysis of interactions of this pathway with other cellular signals corroborating organ size control is limited in part due to the difficulties associated with development of rodent models. Methods Here, we develop a new model of reversible induction of the liver size in mice using siRNA-nanoparticles targeting two kinases of Hippo pathway, namely, mammalian Ste20 family kinases 1 and 2 (Mst1 and Mst2), and an upstream regulator, neurofibromatosis type II (NF2). Results The triple siRNAs nanoparticle-induced hepatomegaly in mice phenocopies one observed with Mst1-/- Mst2-/- liver-specific depletion, as shown by extensive proliferation of hepatocytes and activation of Yap1. The simultaneous co-treatment with a fourth siRNA nanoparticle against Yap1 fully blocked the liver growth. Hippo pathway-induced liver enlargement is associated with p53 activation, evidenced by its accumulation in the nuclei and upregulation of its target genes. Moreover, injections of the triple siRNAs nanoparticle in p53LSL/LSL mice shows that livers lacking p53 expression grow faster and exceed the size of livers in p53 wild type animals, indicating a role of p53 in controlling Yap1-induced liver growth. Conclusion Our data show that siRNA-nanoparticulate manipulation of gene expression can provide the reversible control of organ size in adult animals, which presents a new avenue for the investigation of complex regulatory networks in liver.

show abstract

Phenobarbitone – induced liver response in wild type and in p53 deficient mice

Cited by 4 publications

References 24 publications

Long term phenobarbital administration does not promote the multiplication of hepatocytes replicating after single cyproterone acetate administration

Long term phenobarbital administration does not promote the multiplication of hepatocytes replicating after single cyproterone acetate administration

There are only four basic modes of cell death, although there are many ad-hoc variants adapted to different situations

RNAi-nanoparticulate manipulation of gene expression as a new functional genomics tool in the liver

Contact Info

Product

Resources

About