Disease relevance of Pcna

• CO + HH also increased vascular PCNA and nuclear ssDNA expression compared with hypoxia, suggesting accelerated cell turnover [1].
• The PCNA level had a remarkable decline (53.29+/-1.97) 48 h after ischemia [2].
• The deduced amino acid sequence of rat PCNA/cyclin has a similarity with that of herpes simplex virus type-1 DNA binding protein [3].
• A possible use of enzymatic assays or anti-PCNA antibodies to detect brain tumors is discussed [4].
• In the urinary bladder MMA(V) induced simple hyperplasia and significantly elevated the proliferating cell nuclear antigen (PCNA)-positive index in the urothelium [5].

High impact information on Pcna

• A calmodulin-dependent process is required for cyclin degradation to occur in cell-free extracts prepared from metaphase II-arrested eggs (CSF extracts) when the free Ca2+ concentration is transiently raised in the physiological micromolar range [6].
• This consists of at least two subunits, a polypeptide of relative molecular mass 45,000-62,000 (Mr 45-62K) known as cyclin, and a 34K catalytic subunit which has serine/threonine kinase activity and is known as cdc2 kinase [7].
• The activity of CDK4 is controlled by the opposing effects of the D-type cyclin, an activating subunit, and p16INK4, an inhibitory subunit [8].
• Cyclic AMP inhibited 63 percent of the cells, while the 8-parachlorophenylthio- and 8-benzylthio- analogs of cyclin AMP inhibited the spontaneous firing of 92 and 89 percent of cells, respectively [9].
• Cooperating oncogenes converge to regulate cyclin/cdk complexes [10].

Chemical compound and disease context of Pcna

• PCNA labeling index (LI) and the level of PGE2 in bladder papilloma are much higher than those in normal bladder (P<0.01), but lower than those in bladder TCC (P<0.05) [11].
• The role of G1 cyclin/cdk in Ang II-induced cardiac myocyte hypertrophy by overexpressing cdk inhibitor p21Cip1/Waf1 or p16INK4a was also examined using recombinant adenoviral vectors encoding these genes [12].
• In animals treated with dimethylhydrazine (DMH), crypt hyperplasia, an increased PCNA labeling index, and shifts in both the region of maximal and the upper extent of PCNA expression were observed during DMH exposure; significant crypt hyperplasia and expansion of the PCNA-positive compartment persisted after completion of DMH injections [13].
• Hepatic regeneration and liver dysfunction mirrored these changes; correlations existed between ATP/Pi ratios and [(3)H]thymidine incorporation (r = -0.61, P <.005), PCNA protein expression (r = -0.62, P <.005), and serum bilirubin (r = -0.49, P <.05) [14].
• At 11 days postinjection all animals given PA, whether on probucol or not, developed marked proteinuria with histologically minimal glomerular change and significant increases in intraglomerular monocyte and proliferating cell nuclear antigen counts [15].

Biological context of Pcna

• Renal cell apoptosis and proliferation were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and staining with antibody against proliferating cell nuclear antigen (PCNA), respectively [16].
• PCNA may have contributed to the repair of DNA damage and to cell proliferation caused by exposure to these pollutants [17].
• Borderzone cardiomyocyte cell cycle activation was demonstrated by increased PCNA (40.1+/-2.6 versus 9.3+/-1.1; P<0.0001), Ki-67 (46.3+/-7.2 versus 20.4+/-6.0; P<0.0001), BrdU (44.2+/-13.7 versus 5.2+/-5.2; P<0.05), and phosphohistone-H3 (12.7+/-1.4 versus 0+/-0; P<0.0001) positive cells/hpf [18].
• Because of its possible relationship with cell proliferation, PCNA/cyclin has been receiving attention [3].
• The deduced amino acid sequence and composition of rat PCNA/cyclin are in excellent agreement with the published data [3].

Anatomical context of Pcna

• The PCNA-positive hepatocytes were abundantly localized around the vacuolated and granulomatous legions in both experiments 1 and 2 [19].
• At 48 h, the p27Kip1 suppression still continued in the cortex, while the PCNA-expressing cells appeared mainly around the zona glomerulosa and increased at 72 h [20].
• PCNA positive staining located in goblet cell nuclei [2].
• ITF and PCNA may play an important role in the damage and repair of intestinal mucosa [2].
• Animals were evaluated for weight, mucosal length, and bowel wall muscle thickness on days 4 and 8, and expression of proliferating cell nuclear antigen (PCNA) in intestinal crypt and smooth muscle cells on day 8 [21].

Associations of Pcna with chemical compounds

• TUNEL- and PCNA-positive cells were mainly seen in the tubulointerstitial region of Ang II-infused rats [16].
• Ang II induced increased positivity of TUNEL, and PCNA was blocked completely by losartan, but only partially by hydralazine [16].
• Besides PCNA, GEN effects on the uterine mRNA expression of IGF-1, IGF-1R, Complement C3, estrogen receptor-alpha (ERalpha) and -beta (ERbeta), as well as progesterone receptor were investigated in intact and OVX co-treated animals [22].
• Dex treatment induced shrinkage of adrenals where no PCNA-expressing cells were detected, but most of the cells expressed p27Kip1 [20].
• RESULTS: The basal cells of the GE were actively proliferating, but in the JE, only a few cells were positive for BrdU or PCNA immunostaining [23].

Physical interactions of Pcna

• In conclusion, liver development is associated with a switch from cyclin D2/D3-containing complexes to cyclin D1:CDK4 complexes [24].
• Our data also present more evidence for a strict functional interdependency between G1 cyclin/CDK complexes and c-Myc [25].
• Western assays demonstrated, further, that cyclin D3 was complexed with the cyclin dependent-kinases, cdk2 and cdk4, in differentiated L6 cells [26].
• Application of markers for cell proliferation activities including proliferating cell nuclear antigen (PCNA) and silver-binding nucleolar organizer regions (AgNORs) also revealed significantly elevated AgNOR counts in the long-term group TCC [27].

Regulatory relationships of Pcna

• In fibroblasts, activation of MAPK induces the expression of type D cyclin, whereas, in MCs, this induction has not been shown [28].
• These data show first that Myc controls the activity of G1 cyclin-dependent kinases independently from the transition between quiescence and proliferation and from any effect on cell growth in size [29].
• In androgen-replete rats, proliferating cell nuclear antigen-positive cells co-expressed AR (12.7%), P-ERK (36.4%), and P-ERK + AR (45.0%); 5.9% were probably stimulated by other mitogenic mechanisms [30].
• The results demonstrate that cyclin D1 induction is one of the earlier events in hepatocyte proliferation induced by T3 and suggest that this cyclin might be a common target responsible for the mitogenic activity of ligands of nuclear receptors [31].
• Both S phase entry and activation of cyclin/CDKs were inhibited by over expression of p27 [32].

Other interactions of Pcna

• In experiment 2, numbers (0.65 +/- 0.57 vs 0.17 +/- 0.28 in the 0%) and areas (0.005 +/- 0.005 vs 0.0007 +/- 0.0012 in the 0%) of GST-P-positive foci and hepatocellular proliferating cell nuclear antigen (PCNA) expression (3.8 +/- 2.3 vs 2.6 +/- 0.7 in the 0%) were significantly increased by the 2% treatment [19].
• The following variables were studied: volume fraction (VF) of Bcl-2 immunostaining, percentage of cells immunoreactive to proliferating cell nuclear antigen (LIPCNA) and p53 (LIp53), numerical density of caspase-3 immunoreactive cells (NV caspase-3), and estimates of volume-weighted mean nuclear volume (upsilonV) [33].
• By contrast, significantly stronger beta-catenin and Cyclin D1 mRNA expressions and protein levels were found in CsA-treated rats than controls by RT-PCR and immunohistochemistry at week 4, whereas PCNA production was stronger at both times [34].
• Correlation analyses showed that IMDI had a negative correlation with ITF mRNA and PCNA (r = -0.543, P<0.05; r = -0.794, P<0.01, respectively) [2].
• Samples were also subjected to immunohistochemical analysis for proliferating cell nuclear antigen (PCNA) and caspase 3 [23].

Analytical, diagnostic and therapeutic context of Pcna

• Finally, Cyclin D(1)/Cdk interaction was evaluated by immunoprecipitation [35].
• PCNA expression was measured by immunohistochemistry [2].
• Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin [3].
• Southern blot analysis of total human genomic DNA suggests that there is a single gene coding for PCNA/cyclin [3].
• Examination by immunofluorescence techniques of tracheal cell cultures after exposure to very low doses of alpha particles revealed a large proportion of cells with proliferating cell nuclear antigen (PCNA) bound in their nuclei [36].

References