Regulation of hepatic growth

1986 ◽  
Vol 66 (3) ◽  
pp. 499-541 ◽  
Author(s):  
M. R. Alison
Keyword(s):  
Cell Mass ◽  
Growth Inhibitor ◽  
Cell Loss ◽  
Regenerative Process ◽  
Chemical Mechanism ◽  
Cell Renewal ◽  
Minimal Cell ◽  
Liver Size ◽  
Success Stories ◽  
Isolation And Characterization

The liver is a conditional renewal system, which in the adult organism undergoes minimal cell production and/or cell renewal. However, a reduction in liver cell mass, because of either actual cell loss or cell atrophy, evokes a rapid regenerative response tailored to replace the lost tissue. Synthesis of DNA begins as early as 15 h after a two-thirds hepatectomy, and the fact that all the remaining hepatocytes enter DNA synthesis within the next 48 h does indicate they are all potentially proliferative, and it is unlikely that a distinct stem cell compartment exists. The temporal sequelae of events can be best explained by the semisynchronous passage of cells from G0 into the proliferative cycle (see Fig. 2) where they undergo one or more rounds of cell division before decycling back into the proliferatively quiescent G0 state. The age of the animal and its nutritional and hormonal status are all important modifiers of the response, but none of them is critical to the regenerative process. Experiments involving the administration of sera or the transfer of blood between animals strongly favor the existence of humoral regulatory factors; the liver is apparently capable of producing both inhibitory and stimulatory molecules that act by negative and positive feedback mechanisms, respectively, to control tissue homeostasis, whereas other organs, notably the pancreas, are important sources of facilitatory molecules. A chemical mechanism of self inhibition is a very intellectually appealing hypothesis, but at present there is no consistent message as to the identity of the inhibitory molecule, although most studies suggest the target site for its action is the G1-S transition. Unless the whole field is one of multilateral analysis of an artifact, then endogenous growth inhibitors do exist, but the problem now is one of biochemical isolation and characterization. The field compares rather badly with the many success stories in recent years in which new hormones and peptides have been speedily isolated and purified. A reduction in liver size appears to be associated with a decrease in the concentration of an hepatic growth inhibitor and the production and/or unmasking of a stimulatory factor(s) that is also of hepatic origin. Once again, there is little information about the biochemical nature of the principle and much less on its mode of action. We all assume that such stimulators, and for that matter inhibitors as well, act on "restriction points" or "mitosis operons" and so on.(ABSTRACT TRUNCATED AT 400 WORDS)

Harnessing immune cells to enhance β-cell mass in type 1 diabetes

2016 ◽  
Vol 64 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Ercument Dirice ◽  
Rohit N Kulkarni
Keyword(s):  
Type 1 Diabetes ◽  
Mononuclear Cells ◽  
Islet Cells ◽  
Cell Mass ◽  
Cell Loss ◽  
Cell Types ◽  
Β Cells ◽  
Β Cell ◽  
Autoimmune Attack

Type 1 diabetes is characterized by early β-cell loss leading to insulin dependence in virtually all patients with the disease in order to maintain glucose homeostasis. Most studies over the past few decades have focused on limiting the autoimmune attack on the β cells. However, emerging data from patients with long-standing diabetes who continue to harbor functional insulin-producing cells in their diseased pancreas have prompted scientists to examine whether proliferation of existing β cells can be enhanced to promote better glycemic control. In support of this concept, several studies indicate that mononuclear cells that infiltrate the islets have the capacity to trigger proliferation of islet cells including β cells. These observations indicate the exciting possibility of identifying those mononuclear cell types and their soluble factors and harnessing their ability to promote β-cell growth concomitant with autoimmune therapy to prevent the onset and/or halt the progression of the disease.

scholarly journals Parallel reaction pathways and noncovalent intermediates in thymidylate synthase revealed by experimental and computational tools

2018 ◽  
Vol 115 (41) ◽  
pp. 10311-10314 ◽  
Author(s):  
Svetlana A. Kholodar ◽  
Ananda K. Ghosh ◽  
Katarzyna Świderek ◽  
Vicent Moliner ◽  
Amnon Kohen
Keyword(s):  
Thymidylate Synthase ◽  
Critical Role ◽  
Chemical Mechanism ◽  
Reaction Pathways ◽  
Computational Tools ◽  
Isolation And Characterization ◽  
Dna Biosynthesis ◽  
Energy Surfaces ◽  
Covalent Intermediate

Thymidylate synthase was one of the most studied enzymes due to its critical role in molecular pathogenesis of cancer. Nevertheless, many atomistic details of its chemical mechanism remain unknown or debated, thereby imposing limits on design of novel mechanism-based anticancer therapeutics. Here, we report unprecedented isolation and characterization of a previously proposed intact noncovalent bisubstrate intermediate formed in the reaction catalyzed by thymidylate synthase. Free-energy surfaces of the bisubstrate intermediates interconversions computed with quantum mechanics/molecular mechanics (QM/MM) methods and experimental assessment of the corresponding kinetics indicate that the species is the most abundant productive intermediate along the reaction coordinate, whereas accumulation of the covalent bisubstrate species largely occurs in a parallel nonproductive pathway. Our findings not only substantiate relevance of the previously proposed noncovalent intermediate but also support potential implications of the overstabilized covalent intermediate in drug design targeting DNA biosynthesis.

scholarly journals Persistent Cloaca and Caudal Spinal Agenesis in Calves: Three Cases

1996 ◽  
Vol 33 (6) ◽  
pp. 711-712 ◽  
Author(s):  
C. E. Dean ◽  
C. K. Cebra ◽  
A. A. Frank
Keyword(s):  
Vertebral Column ◽  
Cell Mass ◽  
Spinal Column ◽  
Cell Loss ◽  
Careful Examination ◽  
Persistent Cloaca ◽  
Spinal Lesions ◽  
Column Formation ◽  
Newborn Calves ◽  
Neonatal Calves

Three newborn calves were affected by caudal spinal dysgenesis or agenesis (coccygeal vertebra) and persistent cloaca. The cloacas were lined by a mixture of transitional and colonic epithelium. The vertebral column of one calf was internalized into the cloaca. The association of persistent cloaca and caudal spinal anomalies is thought to be related to cell loss in the caudal cell mass, which affects caudal spinal column formation and cleavage of the cloaca by the urorectal septum. This association is well documented in humans and has been reported in Manx cats. By extrapolation, it appears likely to exist also in neonatal calves. Identification of cloacal lesions in neonatal animals should be cause for careful examination of the vertebral column because many of the associated spinal lesions are occult.

Isolation and characterization of permanent cell lines from inner cell mass cells of bovine blastocysts

1995 ◽  
Vol 40 (4) ◽  
pp. 444-454 ◽  
Author(s):  
Annelies E. P. Van Stekelenburg-Hamers ◽  
Tanja A. E. Van Achterberg ◽  
Heggert G. Rebel ◽  
Jacques E. Fléchon ◽  
Keith H. S. Campbell ◽  
...  
Keyword(s):  
Cell Lines ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Isolation And Characterization ◽  
Permanent Cell

scholarly journals Protein over-expression in Escherichia coli triggers adaptation analogous to antimicrobial resistance

2020 ◽  
Author(s):  
Jack James ◽  
Benjamin Yarnall ◽  
Andy Koranteng ◽  
Jane Gibson ◽  
Tahmina Rahman ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Expression System ◽  
Cell Mass ◽  
Cell Loss ◽  
Integral Membrane Protein ◽  
Large White ◽  
Over Expression ◽  
E Coli ◽  
Pet System ◽  
High Level

Abstract Background: The E. coli pET system is the most widely used protein over-expression system worldwide. It relies on the assumption that all cells produce target protein and it is generally believed that integral membrane protein (IMP) over-expression is more toxic than their soluble counterparts. Results: Using GFP-tagged proteins, high level over-expression of either soluble or IMP targets results in > 99.9 % cell loss with survival rate of only < 0.03 %. Selective pressure generates three phenotypes: large green, large white and small colony variants. As a result, in overnight cultures, ~50 % of the overall cell mass produces no protein. Genome sequencing of the phenotypes revealed genomic mutations that causes either the loss of T7 RNAP activity or its transcriptional downregulation. The over-expression process is bactericidal and is observed for both soluble and membrane proteins.Conclusions: We demonstrate that it is the act of high-level over-expression of exogenous proteins in E. coli that sets in motion a chain of events leading to > 99.9 % cell death. These results redefine our understanding of protein over-production and link it to the adaptive survival response seen in the development of antimicrobial resistance.

scholarly journals Isolation and characterization of Acetobacter aceti from rotten papaya

2016 ◽  
Vol 13 (2) ◽  
pp. 299-306 ◽  
Author(s):  
J Kowser ◽  
MG Aziz ◽  
MB Uddin
Keyword(s):  
Cell Mass ◽  
Single Pair ◽  
Acetobacter Aceti ◽  
Biochemical Tests ◽  
Isolation And Characterization ◽  
The Media ◽  
Durham Tube ◽  
Successive Subculture ◽  
Dry Cell

The present study was concerned with the isolation and characterization of Acetobacter aceti from rotten papaya for vinegar production. The samples were inoculated in sterilized GYC standard media and then incubated at 30°C for 48 hours. Successive subculture was performed to screen out the strains. In Gram’s staining, the morphology of the isolated bacteria exhibited pink, small rod shaped single, pair and chain in arrangement, in the hanging drops technique, all the isolates revealed motile. Biochemical tests were performed by fermentation of five basic sugars by producing both acid and gas bubbles in Durham tube. All of the isolates were Indole, Voges-Proskauer (VP) and Oxidase negative, Methyl Red (MR) and Catalase positive. The growth rate of isolated strain was optimized by weighing dry cell and turbidity at 600 nm at different concentrations of dextrose (1%, 5% and 10%). Ten (10) percent dextrose solution showed rapid growth and higher cell mass than 5% and 1% solution respectively. Acidity of the media gradually increased from 0.102% to 2.18% from day 0 to day 7 and pH of the media decreased from 6.8 to 5.5 during the period. This protocol was successful for enriching Acetobacter aceti, which was essential for vinegar production.J. Bangladesh Agril. Univ. 13(2): 299-306, December 2015

scholarly journals CHOP Contributes to, But Is Not the Only Mediator of, IAPP Induced β-Cell Apoptosis

2016 ◽  
Vol 30 (4) ◽  
pp. 446-454 ◽  
Author(s):  
T. Gurlo ◽  
J. F. Rivera ◽  
A. E. Butler ◽  
M. Cory ◽  
J. Hoang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Protein Misfolding ◽  
Nuclear Translocation ◽  
Cell Mass ◽  
Cell Loss ◽  
Β Cell ◽  
Islet Amyloid

The islet in type 2 diabetes is characterized by β-cell loss, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). When protein misfolding protective mechanisms are overcome, human IAPP (h-IAPP) forms membrane permeant toxic oligomers that induce β-cell dysfunction and apoptosis. In humans with type 2 diabetes (T2D) and mice transgenic for h-IAPP, endoplasmic reticulum (ER) stress has been inferred from nuclear translocation of CCAAT/enhancer-binding protein homologous protein (CHOP), an established mediator of ER stress. To establish whether h-IAPP toxicity is mediated by ER stress, we evaluated diabetes onset and β-cell mass in h-IAPP transgenic (h-TG) mice with and without deletion of CHOP in comparison with wild-type controls. Diabetes was delayed in h-TG CHOP−/− mice, with relatively preserved β-cell mass and decreased β-cell apoptosis. Deletion of CHOP attenuates dysfunction of the autophagy/lysosomal pathway in β-cells of h-TG mice, uncovering a role for CHOP in mediating h-IAPP-induced dysfunction of autophagy. As deletion of CHOP delayed but did not prevent h-IAPP-induced β-cell loss and diabetes, we examined CHOP-independent stress pathways. JNK, a target of the IRE-1pTRAF2 complex, and the Bcl-2 family proapoptotic mediator BIM, a target of ATF4, were comparably activated by h-IAPP expression in the presence and absence of CHOP. Therefore, although these studies affirm that CHOP is a mediator of h-IAPP-induced ER stress, it is not the only one. Therefore, suppression of CHOP alone is unlikely to be a durable therapeutic strategy to protect against h-IAPP toxicity because multiple stress pathways are activated.

scholarly journals One year of sitagliptin treatment protects against islet amyloid-associated β-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice

2013 ◽  
Vol 305 (4) ◽  
pp. E475-E484 ◽  
Author(s):  
Kathryn Aston-Mourney ◽  
Shoba L. Subramanian ◽  
Sakeneh Zraika ◽  
Thanya Samarasekera ◽  
Daniel T. Meier ◽  
...  
Keyword(s):  
Exocrine Pancreas ◽  
Cell Mass ◽  
Cell Loss ◽  
Amyloid Deposition ◽  
Amyloid Formation ◽  
Metformin Treatment ◽  
Cell Toxicity ◽  
Β Cell ◽  
Islet Amyloid

The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve β-cell mass. However, sitagliptin also increases β-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated β-cell toxicity. Conversely, metformin treatment decreases islet amyloid formation by decreasing β-cell secretory demand and could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin treatment has also been reported to be detrimental to the exocrine pancreas. We investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and β-cell toxicity and induced pancreatic ductal proliferation, pancreatitis, and/or pancreatic metaplasia/neoplasia. hIAPP transgenic and nontransgenic littermates were followed for 1 yr on no treatment, sitagliptin, metformin, or the combination. Islet amyloid deposition, β-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. Relative to untreated mice, sitagliptin treatment did not increase amyloid deposition, despite increasing hIAPP release, and prevented amyloid-induced β-cell loss. Metformin treatment alone or with sitagliptin decreased islet amyloid deposition to a similar extent vs untreated mice. Ductal proliferation was not altered among treatment groups, and no evidence of pancreatitis, ductal metaplasia, or neoplasia were observed. Therefore, long-term sitagliptin treatment stimulates β-cell secretion without increasing amyloid formation and protects against amyloid-induced β-cell loss. This suggests a novel effect of sitagliptin to protect the β-cell in type 2 diabetes that appears to occur without adverse effects on the exocrine pancreas.

Sign in / Sign up

Export Citation Format

Share Document