Cellular aspects of pathogenesis of hypertrophic cardiomyopathy: Role of cardiomyocyte polyploidy and activation of nuclear antigen of the proliferating cell in myocardium

2007 ◽  
Vol 1 (6) ◽  
pp. 582-588 ◽  
Author(s):  
E. V. Shlyakhto ◽  
L. A. Bokeria ◽  
M. G. Rybakova ◽  
E. N. Semernin ◽  
G. V. Selivanova ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Nuclear Antigen ◽  
Proliferating Cell

scholarly journals Inhibition of let-7c Regulates Cardiac Regeneration after Cryoinjury in Adult Zebrafish

2019 ◽  
Vol 6 (2) ◽  
pp. 16 ◽  
Author(s):  
Suneeta Narumanchi ◽  
Karri Kalervo ◽  
Sanni Perttunen ◽  
Hong Wang ◽  
Katariina Immonen ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Regeneration ◽  
Nuclear Antigen ◽  
Heart Regeneration ◽  
Adult Zebrafish ◽  
Tissue Samples ◽  
Micro Rnas ◽  
Proliferating Cell ◽  
Zebrafish Heart

The let-7c family of micro-RNAs (miRNAs) is expressed during embryonic development and plays an important role in cell differentiation. We have investigated the role of let-7c in heart regeneration after injury in adult zebrafish. let-7c antagomir or scramble injections were given at one day after cryoinjury (1 dpi). Tissue samples were collected at 7 dpi, 14 dpi and 28 dpi and cardiac function was assessed before cryoinjury, 1 dpi, 7 dpi, 14 dpi and 28 dpi. Inhibition of let-7c increased the rate of fibrinolysis, increased the number of proliferating cell nuclear antigen (PCNA) positive cardiomyocytes at 7 dpi and increased the expression of the epicardial marker raldh2 at 7 dpi. Additionally, cardiac function measured with echocardiography recovered slightly more rapidly after inhibition of let-7c. These results reveal a beneficial role of let-7c inhibition in adult zebrafish heart regeneration.

scholarly journals Multi-Omics Integration Highlights the Role of Ubiquitination in CCl4-Induced Liver Fibrosis

2020 ◽  
Vol 21 (23) ◽  
pp. 9043
Author(s):  
Maria Mercado-Gómez ◽  
Fernando Lopitz-Otsoa ◽  
Mikel Azkargorta ◽  
Marina Serrano-Maciá ◽  
Sofia Lachiondo-Ortega ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Function ◽  
Gene Array ◽  
Matrix Proteins ◽  
Nuclear Antigen ◽  
Post Translational Modification ◽  
Physiological Processes ◽  
Ubiquitin System ◽  
Proliferating Cell

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in chronic liver disease. Ubiquitination is a post-translational modification that is crucial for a plethora of physiological processes. Even though the ubiquitin system has been implicated in several human diseases, the role of ubiquitination in liver fibrosis remains poorly understood. Here, multi-omics approaches were used to address this. Untargeted metabolomics showed that carbon tetrachloride (CCl4)-induced liver fibrosis promotes changes in the hepatic metabolome, specifically in glycerophospholipids and sphingolipids. Gene ontology analysis of public deposited gene array-based data and validation in our mouse model showed that the biological process “protein polyubiquitination” is enriched after CCl4-induced liver fibrosis. Finally, by using transgenic mice expressing biotinylated ubiquitin (bioUb mice), the ubiquitinated proteome was isolated and characterized by mass spectrometry in order to unravel the hepatic ubiquitinated proteome fingerprint in CCl4-induced liver fibrosis. Under these conditions, ubiquitination appears to be involved in the regulation of cell death and survival, cell function, lipid metabolism, and DNA repair. Finally, ubiquitination of proliferating cell nuclear antigen (PCNA) is induced during CCl4-induced liver fibrosis and associated with the DNA damage response (DDR). Overall, hepatic ubiquitome profiling can highlight new therapeutic targets for the clinical management of liver fibrosis.

Role of AT1 angiotensin II receptors in renal ischemic injury

1998 ◽  
Vol 274 (1) ◽  
pp. F79-F90 ◽  
Author(s):  
Jimmy Kontogiannis ◽  
Kevin D. Burns
Keyword(s):  
Serum Creatinine ◽  
Ischemia Reperfusion ◽  
Renin Angiotensin System ◽  
Ischemic Injury ◽  
Nuclear Antigen ◽  
Ang Ii ◽  
Receptor Mrna ◽  
Proximal Tubular ◽  
Proliferating Cell

The present studies determined the effect of renal ischemia/reperfusion on components of the intrarenal renin-angiotensin system in rats and evaluated the effect of AT1angiotensin (ANG) II receptor blockade on functional recovery. After bilateral renal pedicle occlusion for 60 min, serum creatinine increased, peaking at 72 h, and returned to sham levels after 120 h. ANG II levels in ischemic kidneys were significantly increased 24 h after reperfusion but did not differ from levels in sham kidneys after 120 h. Both renal cortical angiotensinogen mRNA and proximal tubular AT1 receptor mRNA were significantly reduced early after reperfusion, returning to sham levels by 120 and 72 h, respectively. AT2ANG II receptor mRNA was undetectable in proximal tubules from sham rats but was consistently present in ischemic rats at 120 h. By histoautoradiography, we found that binding of125I-labeled ANG II was preserved in glomeruli but was decreased in whole cortex and outer medulla early after reperfusion and was completely blocked by the AT1 antagonist losartan. Treatment of rats with losartan (25 mg/kg sc daily), starting at the time of reperfusion, had no effect on expression of proliferating cell nuclear antigen in cortical tubules but caused a significant decrease in serum creatinine at 72 h (ischemia: 334 ± 69 μM vs. ischemia + losartan: 135 ± 28 μM; P < 0.025, n = 6). These data indicate that renal ischemic injury causes an early increase in intrarenal ANG II levels, associated with reduction of mRNA for angiotensinogen and proximal tubular AT1 receptors, and maintenance of glomerular ANG II binding. Losartan accelerates recovery of renal function, suggesting that activation of AT1 receptors impairs glomerular filtration in the postischemic kidney.

Characterization of cytosolic proliferating cell nuclear antigen (PCNA) in neutrophils: antiapoptotic role of the monomer

2013 ◽  
Vol 94 (4) ◽  
pp. 723-731 ◽  
Author(s):  
Alessia De Chiara ◽  
Magali Pederzoli-Ribeil ◽  
Julie Mocek ◽  
Céline Candalh ◽  
Patrick Mayeux ◽  
...  
Keyword(s):  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Proliferating Cell

scholarly journals Role of Intrasplenic Hepatocyte Transplantation in Improving Survival and Liver Regeneration after Hepatic Resection in Cirrhotic Rats

2002 ◽  
Vol 11 (5) ◽  
pp. 399-402 ◽  
Author(s):  
Tarik A. Ahmad ◽  
Susumu Eguchi ◽  
Katsuhiko Yanaga ◽  
Shungo Miyamoto ◽  
Yukio Kamohara ◽  
...  
Keyword(s):  
Hepatic Resection ◽  
Transforming Growth Factor ◽  
Hepatocyte Transplantation ◽  
Nuclear Antigen ◽  
Liver Growth ◽  
Group I ◽  
Group Ii ◽  
Proliferating Cell ◽  
Tgf Β1

We studied the effect of preoperative hepatocyte transplantation on the prevention of liver failure in cirrhotic rats after hepatic resection. Two groups of Lewis rats were rendered cirrhotic by IP injection of 1% dimethylnitrosamine and were subjected to 33% hepatectomy. Two days before the resection, 36 rats in group I received intrasplenic hepatocyte transplantation, and 25 rats in group II were given intrasplenic injection of normal saline as a control. By the end of the third postoperative day, the rats in group I had better survival and a better biochemical profile than those in group II. The liver growth rate and the labeling index of proliferating cell nuclear antigen (PCNA-LI) showed a steady rise in group I. Compared with group II, group I had a significantly lower transforming growth factor (TGF-β1) level (p < 0.05). We conclude that preoperative intrasplenic hepatocyte transplantation improves survival and facilitates regeneration in cirrhotic rats after hepatic resection.

scholarly journals A/T mutagenesis in hypermutated immunoglobulin genes strongly depends on PCNAK164 modification

2007 ◽  
Vol 204 (8) ◽  
pp. 1989-1998 ◽  
Author(s):  
Petra Langerak ◽  
Anders O.H. Nygren ◽  
Peter H.L. Krijger ◽  
Paul C.M. van den Berk ◽  
Heinz Jacobs
Keyword(s):  
B Cells ◽  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Nuclear Antigen ◽  
Translesion Dna Synthesis ◽  
Class Switch ◽  
Activation Induced Cytidine Deaminase ◽  
Mismatch Recognition ◽  
Proliferating Cell

B cells use translesion DNA synthesis (TLS) to introduce somatic mutations around genetic lesions caused by activation-induced cytidine deaminase. Monoubiquitination at lysine164 of proliferating cell nuclear antigen (PCNAK164) stimulates TLS. To determine the role of PCNAK164 modifications in somatic hypermutation, PCNAK164R knock-in mice were generated. PCNAK164R/K164R mutants are born at a sub-Mendelian frequency. Although PCNAK164R/K164R B cells proliferate and class switch normally, the mutation spectrum of hypermutated immunoglobulin (Ig) genes alters dramatically. A strong reduction of mutations at template A/T is associated with a compensatory increase at G/C, which is a phenotype similar to polymerase η (Polη) and mismatch repair–deficient B cells. Mismatch recognition, monoubiquitinated PCNA, and Polη likely cooperate in establishing mutations at template A/T during replication of Ig genes.

scholarly journals Somatic hypermutation of immunoglobulin genes: lessons from proliferating cell nuclear antigen K164R mutant mice

2008 ◽  
Vol 364 (1517) ◽  
pp. 621-629 ◽  
Author(s):  
Petra Langerak ◽  
Peter H.L Krijger ◽  
Marinus R Heideman ◽  
Paul C.M van den Berk ◽  
Heinz Jacobs
Keyword(s):  
B Cells ◽  
Proliferating Cell Nuclear Antigen ◽  
Somatic Mutations ◽  
Dna Polymerases ◽  
Critical Role ◽  
Dna Lesions ◽  
Nuclear Antigen ◽  
Immunoglobulin Genes ◽  
Proliferating Cell

Proliferating cell nuclear antigen (PCNA) encircles DNA as a ring-shaped homotrimer and, by tethering DNA polymerases to their template, PCNA serves as a critical replication factor. In contrast to high-fidelity DNA polymerases, the activation of low-fidelity translesion synthesis (TLS) DNA polymerases seems to require damage-inducible monoubiquitylation (Ub) of PCNA at lysine residue 164 (PCNA-Ub). TLS polymerases can tolerate DNA damage, i.e. they can replicate across DNA lesions. The lack of proofreading activity, however, renders TLS highly mutagenic. The advantage is that B cells use mutagenic TLS to introduce somatic mutations in immunoglobulin (Ig) genes to generate high-affinity antibodies. Given the critical role of PCNA-Ub in activating TLS and the role of TLS in establishing somatic mutations in immunoglobulin genes, we analysed the mutation spectrum of somatically mutated immunoglobulin genes in B cells from PCNA K164R knock-in mice. A 10-fold reduction in A/T mutations is associated with a compensatory increase in G/C mutations—a phenotype similar to Polη and mismatch repair-deficient B cells. Mismatch recognition, PCNA-Ub and Polη probably act within one pathway to establish the majority of mutations at template A/T. Equally relevant, the G/C mutator(s) seems largely independent of PCNA K164 modification.

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