Quercetin inhibited DNA synthesis and induced apoptosis associated with increase in c-fos mRNA level and the upregulation of p21WAF1CIP1 mRNA and protein expression during liver regeneration after partial hepatectomy

1999 ◽  
Vol 1427 (1) ◽  
pp. 112-120 ◽  
Author(s):  
Kumiko Iwao ◽  
Ikuyo Tsukamoto
Keyword(s):  
Protein Expression ◽  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Mrna Level ◽  
Mrna And Protein Expression ◽  
Induced Apoptosis

scholarly journals Yiqi Huoxue Recipe Improves Liver Regeneration in Rats after Partial Hepatectomy via JNK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Wen-cong Li ◽  
Su-xian Zhao ◽  
Wei-guang Ren ◽  
Hui-juan Du ◽  
Yu-guo Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Protective Effects ◽  
Jnk Pathway ◽  
Expression Levels ◽  
Protein Levels ◽  
Mrna And Protein Expression

The liver is the only visceral organ that exhibits a remarkable capability of regenerating in response to partial hepatectomy (PH) or chemical injury. Improving liver regeneration (LR) ability is the basis for the favourable treatment outcome of patients after PH, which can serve as a potential indicator for postoperative survival. The present study aimed to investigate the protective effects of Yiqi Huoxue recipe (YQHX) on LR after PH in rats and further elucidate its underlying mechanism. A two-thirds PH rat model was used in this study. Wistar rats were randomly divided into four groups: sham-operated, PH, YQHX + PH, and Fuzheng Huayu decoction (FZHY) + PH groups. All rats were sacrificed under anesthesia at 24 and 72 h after surgery. The rates of LR were calculated, and the expression levels of cyclin D1 and c-jun were determined by immunohistochemical staining. The protein levels of p-JNK1/2, JNK1/2, p-c-jun, c-jun, Bax, and Bcl-2 were detected by Western blotting, while the mRNA levels of JNK1, JNK2, c-jun, Bax, and Bcl-2 were examined by real-time polymerase chain reaction (RT-PCR). At the corresponding time points, YQHX and FZHY administration dramatically induced the protein levels of p-JNK1/2 compared to the PH group p<0.05, while FZHY + PH group showed prominently increase in p-JNK1/2 protein levels compared to the YQHX + PH group p<0.05. A similar trend was observed for the expression levels of p-c-jun. Compared to the PH group, YQHX and FZHY markedly reduced the mRNA and protein expression levels of Bax at 24 h after PH, while those in the FZHY + PH group decreased more obviously p<0.05. Besides, in comparison with the PH group, YQHX and FZHY administration predominantly upregulated the mRNA and protein expression levels of Bcl-2 at 24 and 72 h after PH p<0.05. In conclusion, YQHX improves LR in rats after PH by inhibiting hepatocyte apoptosis via the JNK signaling pathway.

DEOXYCYTIDYLATE DEAMINASE LEVELS IN REGENERATING RAT LIVER

1961 ◽  
Vol 39 (6) ◽  
pp. 1043-1054 ◽  
Author(s):  
D. K. Myers ◽  
C. Anne Hemphill ◽  
Constance M. Townsend
Keyword(s):  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Deoxyribonucleic Acid ◽  
Regenerating Liver ◽  
Regenerating Rat Liver ◽  
High Level ◽  
Early Regeneration

Deoxycytidylate deaminase activity and net synthesis of deoxyribonucleic acid (DNA) in vivo were found to increase at approximately the same time during the early stages of liver regeneration. However, deaminase activity in the regenerating liver remained at a high level for 1 day after DNA synthesis had slowed down again during the later stages of regeneration. The increase in deaminase activity was restricted as a result of exposure to 600 r X radiation during early regeneration, but this effect only became evident 11–16 hours after the irradiation. Irradiation on the second day after partial hepatectomy, when deaminase levels in control regenerating livers were relatively constant, failed to affect the deaminase activity immediately but did produce a 40–50% decrease in activity 11–16 hours later. Other antimitotic agents, e.g., colchicine, had little effect on deaminase activity.

scholarly journals Expression Characteristics and Significant Prognostic Values of PGK1 in Breast Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Yanping Li ◽  
Shanshan Wang ◽  
Xiaoyuan Zhang ◽  
Rui Yang ◽  
Xiaonan Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Mrna Level ◽  
Vital Role ◽  
Migration And Invasion ◽  
Breast Cancer Patients ◽  
Clinicopathologic Characteristics ◽  
Independent Prognostic Marker ◽  
Potential Biomarker ◽  
Mrna And Protein Expression

It was proven that PGK1 plays a vital role in the proliferation, migration, and invasion of human breast cancer. However, the correlation of PGK1 mRNA and protein expression with clinicopathologic characteristics and prognostic values according to various kinds of breast cancer patient classifications remains unsufficient. Here, we analyzed data from the Oncomine database, Breast cancer Gene-Expression Miner v4.5, TNMplot, MuTarget, PrognoScan database, and clinical bioinformatics to investigate PGK1 expression distribution and prognostic value in breast cancer patients. Our study revealed that the mRNA and protein expression levels of PGK1 were up-regulated in various clinicopathologic types of breast cancer. Moreover, the expression of PGK1 was correlated with mutations of common tumor suppressor genes TP53 and CDH1. In addition, we found that high mRNA level of PGK1 was significantly associated with poor OS, RFS, and DMFS. Notably, Cox regressionanalysis showed that PGK1 could be used as an independent prognostic marker. In summary, the aforementioned findings suggested that PGK1 might be not only explored as a potential biomarker, but also combined with TP53/CDH1 for chemotherapy in breast cancer.

Effect of thyroparathyroidectomy on the activities of thymidylate synthetase and thymidine kinase during liver regeneration after partial hepatectomy

1987 ◽  
Vol 72 (4) ◽  
pp. 455-461 ◽  
Author(s):  
Rieko Nakata ◽  
Ikuyo Tsukamoto ◽  
Masamitsu Miyoshi ◽  
Shosuke Kojo
Keyword(s):  
Dna Synthesis ◽  
Liver Regeneration ◽  
Time Dependence ◽  
Thymidine Kinase ◽  
Partial Hepatectomy ◽  
Dna Content ◽  
Thymidylate Synthetase ◽  
High Dose ◽  
Regenerating Liver ◽  
Relative Contribution

1. Thyroparathyroidectomy (TPTX) carried out at 72 h before partial hepatectomy (PH) reduced the induction of hepatic thymidylate synthetase (TS) and thymidine kinase (TK), which are rate-determining enzymes in DNA synthesis, at 24 h after PH. 2. When TPTX was carried out at 24 h before PH, TK activity at 24 h after PH was not reduced at all, yet TS activity was reduced significantly. Thus the effect of TPTX differed in time dependence between TS and TK. 3. The depression of TK activity in rats which were subjected to TPTX at 72 h before PH, was recovered by Ca2+ supplementation. This result demonstrated that the rise of TK activity in regenerating liver is regulated by plasma Ca2+. 4. Since a high dose of tri-iodothyronine (T3) was required to cause elevation of the activities of these enzymes and DNA content in 24 h-regenerating liver of TPTX rats, the relative contribution of T3 to liver regeneration may be small.

Restriction of gut-derived endotoxin impairs DNA synthesis for liver regeneration

1985 ◽  
Vol 249 (5) ◽  
pp. R563-R569 ◽  
Author(s):  
R. P. Cornell
Keyword(s):  
Liver Resection ◽  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Lipid A ◽  
Subcutaneous Administration ◽  
Endotoxin Tolerance ◽  
Polymyxin B ◽  
Gram Negative Bacteria ◽  
Higher Doses

The influence of restricting gut-derived endotoxin availability on liver regeneration after partial hepatectomy was evaluated. Partial hepatectomy was performed by 67% liver resection of ether-anesthetized rats. Liver regeneration was quantified after partial hepatectomy by [3H]thymidine incorporation into hepatic DNA; endotoxemia due to absorption of endogenous endotoxin from the gut into the portal circulation was determined by qualitative lysate assay of perchloric acid-extracted plasma samples, and plasma levels of the hepatotrophic factors insulin and glucagon were measured by radioimmunoassay. Treatments to restrict gut-derived endotoxin included chronic gavage with neomycin and cefazolin for gut sterilization, chronic gavage with cholestyramine to bind endotoxin within the gut, subcutaneous administration of polymyxin B to neutralize the lipid A portion of circulating endotoxin, intraperitoneal induction of endotoxin tolerance by progressively higher doses of endotoxin, and experimentation with isolator-reared defined flora Fisher rats that were Gram-negative bacteria deficient and therefore endotoxin deficient. All treatments to restrict endogenous endotoxin impaired DNA synthesis in regenerating livers particularly 21 h posthepatectomy when replication was increasing most rapidly in normal rats. We hypothesize that impairment of DNA synthesis after partial hepatectomy in endotoxin-restricted animals was due to the observed lack of normal systemic endotoxemic as well as hyperinsulinemic and hyperglucagonemic responses to 67% liver resection.

scholarly journals MicroRNA-204-5p regulates apoptosis by targeting Bcl2 in rat ovarian granulosa cells exposed to cadmium†

2020 ◽  
Vol 103 (3) ◽  
pp. 608-619
Author(s):  
Ping Zhong ◽  
Jin Liu ◽  
Hong Li ◽  
Senbin Lin ◽  
Lingfeng Zeng ◽  
...  
Keyword(s):  
Protein Expression ◽  
Granulosa Cells ◽  
B Cell Lymphoma ◽  
Experimental Conditions ◽  
Expression Levels ◽  
Ovarian Granulosa Cells ◽  
Mrna And Protein Expression ◽  
Induced Apoptosis ◽  
Apoptosis Regulation

Abstract This study aimed to investigate whether cadmium (Cd) cytotoxicity in rat ovarian granulosa cells (OGCs) is mediated through apoptosis or autophagy and to determine the role of microRNAs (miRNAs) in Cd cytotoxicity. To test this hypothesis, rat OGCs were exposed to 0, 10, and 20 μM CdCl2 in vitro. As the Cd concentration increased, OGC apoptosis increased. In addition, Cd promoted apoptosis by decreasing the mRNA and protein expression levels of inhibition of B-cell lymphoma 2 (Bcl2). However, under our experimental conditions, no autophagic changes in rat OGCs were observed, and the mRNA and protein expression levels of the autophagic markers microtubule-associated protein 1 light chain 3 alpha (Map1lc3b) and Beclin1 (Becn1) were not changed. Microarray chip analysis, miRNA screening, and bioinformatics approaches were used to further explore the roles of apoptosis regulation-related miRNAs. In total, 19 miRNAs putatively related to Cd-induced apoptosis in rat OGCs were identified. Notably, miR-204-5p, which may target Bcl2, was identified. Then, rat OGCs were cultured in vitro and used to construct the miR-204-5p-knockdown cell line LV2-short hairpin RNA (shRNA). LV2-shRNA cells were exposed to 20 μM Cd for 12 h, and the mRNA and protein expression levels of Bcl2 were increased. Our findings suggest that Cd is cytotoxic to rat OGCs, and mitochondrial apoptosis rather than autophagy mediates Cd-induced damage to OGCs. Cd also affects apoptosis-related miRNAs, and the underlying apoptotic mechanism may involve the Bcl2 gene.

scholarly journals Discrepancy between Jun/Fos Proto-Oncogene mRNA and Protein Expression in the Rheumatoid Arthritis Synovial Membrane

J ◽  
2020 ◽  
Vol 3 (2) ◽  
pp. 181-194 ◽  
Author(s):  
René Huber ◽  
Bruno Stuhlmüller ◽  
Elke Kunisch ◽  
Raimund W. Kinne
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Expression ◽  
Synovial Membrane ◽  
Rna Binding ◽  
Mrna Level ◽  
Joint Disease ◽  
Protein Levels ◽  
Modifying Factors ◽  
Mrna And Protein Expression ◽  
Joint Trauma

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease characterized by overexpression of pro-inflammatory/pro-destructive mediators, whose regulation has been the focus of our previous studies. Since the expression of these proteins commonly depends on AP-1, the expression of the AP-1-forming subunits cJun, JunB, JunD, and cFos was assessed in synovial membrane (SM) samples of RA, osteoarthritis (OA), joint trauma (JT), and normal controls (NC) using ELISA and qRT-PCR. With respect to an observed discrepancy between mRNA and protein levels, the expression of the mRNA stability-modifying factors AU-rich element RNA-binding protein (AUF)-1, tristetraprolin (TTP), and human antigen R (HuR) was measured. JunB and JunD protein expression was significantly higher in RA-SM compared to OA and/or NC. By contrast, jun/fos mRNA expression was significantly (cjun) or numerically decreased (junB, junD, cfos) in RA and OA compared to JT and/or NC. Remarkably, TTP and HuR were also affected by discrepancies between their mRNA and protein levels, since they were significantly decreased at the mRNA level in RA versus NC, but significantly or numerically increased at the protein level when compared to JT and NC. Discrepancies between the mRNA and protein expression for Jun/Fos and TTP/HuR suggest broad alterations of post-transcriptional processes in the RA-SM. In this context, increased levels of mRNA-destabilizing TTP may contribute to the low levels of jun/fos and ttp/hur mRNA, whereas abundant mRNA-stabilizing HuR may augment translation of the remaining mRNA into protein with potential consequences for the composition of the resulting AP-1 complexes and the expression of AP-1-dependent genes in RA.

scholarly journals Increased expression of the lipocalin 24p3 as an apoptotic mechanism for MK886

2003 ◽  
Vol 372 (1) ◽  
pp. 203-210 ◽  
Author(s):  
Zhimin TONG ◽  
Xuli WU ◽  
James P. KEHRER
Keyword(s):  
Protein Expression ◽  
Protein S ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mrna And Protein Expression ◽  
Induced Apoptosis ◽  
Inhibitor Of Protein Synthesis ◽  
New Protein ◽  
Apoptotic Mechanism

MK886, a strong proapoptotic agent, is an inhibitor of 5-lipoxygenase (LOX) through binding to the 5-LOX-activating protein (FLAP). Although MK886-induced apoptosis is through a FLAP-independent pathway, the precise mechanisms are not understood. In the present study, a possible role of 24p3, a lipocalin, in MK886-induced apoptosis was investigated. Exposure of murine prolymphoid progenitor cells (FL5.12) to 20 μM MK886 for 16 h dramatically increased 24p3 mRNA and protein expression. Induction could also be achieved with another FLAP inhibitor, MK591. The induction of 24p3 by MK886 was dose- and time-dependent. The up-regulated 24p3 mRNA expression by MK886 was enhanced a further 3.1-fold by WY14643, an activator of peroxisome-proliferator-activated receptor α, whereas ciglitazone, an activator of peroxisome-proliferator-activated receptor γ attenuated the MK886-induced 24p3 expression by more than 50%. Neither WY14643 nor ciglitazone alone had any effect on the expression of 24p3. The induction of 24p3 by MK886 was dependent on the synthesis of new protein(s), since cycloheximide, an inhibitor of protein synthesis, prevented this effect. In all cases, including the inhibition of MK886-induced 24p3 protein expression by stable transfection with antisense cDNA of 24p3, the extent of apoptosis closely paralleled 24p3 levels. Apoptosis induced by MK886, or enhanced by WY14643, was accompanied by the cleavage and activation of caspase-3. The overexpression of bcl-2 or bcl-xL in FL5.12 cells inhibited apoptosis induced by MK886 as well as the enhancement of apoptosis by WY14643. Thus 24p3 is an MK886-inducible gene and may play an important role in MK886-induced apoptosis.

Influence of epidermal growth factor on liver regeneration after partial hepatectomy in mice

1991 ◽  
Vol 128 (3) ◽  
pp. 425-431 ◽  
Author(s):  
S. Noguchi ◽  
Y. Ohba ◽  
T. Oka
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Dna Content ◽  
Sharp Peak ◽  
Submandibular Glands ◽  
Total Liver ◽  
Epidermal Growth

ABSTRACT The role of epidermal growth factor (EGF) in liver regeneration was studied in mice after partial hepatectomy. Two weeks before partial hepatectomy, mice were sham-operated (control) or sialoadenectomized (removal of submandibular glands) to reduce plasma EGF levels. Sialoadenectomized mice showed low plasma EGF levels (29·7 ±6·6 pmol/l; mean ± s.e.m.) compared with controls (66·0±8·3 pmol/l). After partial hepatectomy, sialoadenectomized mice were treated with or without a daily s.c. injection of 5 μg EGF and the rate of DNA synthesis in the regenerating liver was monitored by [125I]iododeoxyuridine uptake. Control mice showed a sharp peak of DNA synthesis at 48 h after partial hepatectomy while sialoadenectomized mice showed a delayed and broad peak at 84 h. Treatment of sialoadenectomized mice with EGF (5 μg/mouse per day) completely restored the pattern of DNA synthesis so that a sharp peak appeared at 48 h. The total liver DNA content of the control mice (79·1±2·5% of the preoperative level; mean ± s.e.m.) was significantly (P < 0·01) higher than that of the sialoadenectomized mice (65·2±3·0%) 3 days after partial hepatectomy, but this difference disappeared on day 7 when liver regeneration was almost completed in both groups. Treatment of sialoadenectomized mice with EGF increased total liver DNA content (78·2±2·9%) to that of control mice on day 3 after partial hepatectomy. In addition, normal mice showed a rapid increase in plasma EGF levels at 1–8 h after partial hepatectomy, whereas sialoadenectomized mice showed low plasma EGF levels throughout the course of the experiment. These results suggest that EGF derived from the submandibular glands plays a role in promoting the early stage of liver regeneration. Journal of Endocrinology (1991) 128, 425–431

scholarly journals Modulation of Rat Liver Regeneration after Partial Hepatectomy by Dietary Cholesterol

2018 ◽  
Vol 61 (1) ◽  
pp. 22-28
Author(s):  
Pavel Živný ◽  
Helena Živná ◽  
Vladimír Palička ◽  
Lenka Žaloudková ◽  
Petra Mocková ◽  
...  
Keyword(s):  
Protein Expression ◽  
Dna Synthesis ◽  
Liver Regeneration ◽  
Total Cholesterol ◽  
Dietary Cholesterol ◽  
Ldl Receptor ◽  
Cholesterol Homeostasis ◽  
Serum Total Cholesterol ◽  
Receptor Protein ◽  
Triglyceride Concentration

Introduction: The aim of study was to evaluate impact of long-term dietary cholesterol overload on the cholesterol homeostasis and liver regeneration. Material and Methods: Serum lipid parameters,14C-cholesterol incorporation, liver DNA synthesis and protein expression was determined in partially hepatectomized (PH) rats fed with a standard (SLD) or hypercholesterolemic (CHOL) diet. Results: 29-day intake of CHOL diet before PH produced increase in serum total cholesterol, LDL lipoprotein, and triglyceride concentration. PH provoked decrease in serum total cholesterol and triglyceride concentration in both groups. PH was associated with increase in serum ALT activity more pronounced in CHOL animals. Hepatic DNA synthesis was increased after PH in both groups, but lower in CHOL. Hypercholesterolemic diet reduced the absorption of radiolabelled cholesterol in intestine and then activity in blood and liver. The14C-cholesterol hepatic activities tend to increase after PH in both groups. CHOL diet produced up-regulation of Acyl-CoA:cholesterol acyltransferase-2 protein expression. PH was associated with increase of LDL receptor and Acyl-CoA:cholesterol acyltransferase-2 protein expression in both dietary groups. Discussion: Liver regeneration after PH is negatively influenced by CHOL diet. The increased uptake of cholesterol in the liver after PH associated with up-regulation of LDL receptor protein expression suggests preferential use of extrahepatic cholesterol by the liver.

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