p300/CBP-associated factor (PCAF), a histone acetyltransferase, is involved in many cellular processes such as differentiation, proliferation, apoptosis, and reaction to cell damage by modulating the activities of several genes proteins through acetylation either histones or transcription factors. Here, we examined pathogenic role PCAF its potential novel therapeutic target progression renal tubulointerstitial fibrosis induced non-diabetic unilateral ureteral obstruction (UUO) male C57BL/6...

Epigenetic silencing of RASSF (Ras association domain family) genes RASSF1 and RASSF5 (also called NORE1) by CpG hypermethylation is found frequently in many cancers. Although the physiological roles have been studied some detail, exact functions are not well understood. Here, we show that plays an important role mediating apoptosis response to death receptor ligands, TNF-α TNF-related apoptosis-inducing ligand. Depletion siRNA significantly reduced TNF-α-mediated apoptosis, likely through...

Although it has been suggested that kinesin family member 14 (KIF14) oncogenic potential in various cancers, including hepatocellular carcinoma (HCC), the molecular mechanism of this remains unknown. We aimed to elucidate role KIF14 hepatocarcinogenesis by knocking down HCC cells overexpressed KIF14. After knockdown, changes tumor cell growth, cycle and cytokinesis were examined. also examined regulatory molecules upstream Skp1/Cul1/F-box (SCF) complex molecules. Knockdown resulted...

Primary cilia are sensory organelles that regulate various signaling pathways. When microtubules compared to a highway, motor proteins carry and transport cargo proteins, which tuned by post-translational modifications, such as acetylation. However, the role of acetylation in primary regulation remains unclear. In this study, histone K (lysine) acetyltransferase 2 B (Kat2b) was identified novel regulator cilia. Kat2b, mainly regulates transcription p300/CBP associated factor, is localized...

Treatment of L1210 cells with prostaglandin A 2 (PGA ) or 9‐deoxy‐Δ 9,12 ‐13,14‐dihydro PGD (Δ 12 ‐PGJ resulted in significant G2/M arrest and subsequent DNA fragmentation at concentrations that are cytotoxic to the cells. On agarose gel electrophoresis, ladder formation was evident 24 h after addition Δ remained apparent through 72 h, whereas accumulation observed 6 treatment. When morphology examined by electron microscopy, incubated a dose PGA for showed characteristic morphological...

Besides lowering glucose, empagliflozin, a selective sodium-glucose cotransporter-2 (SGLT2) inhibitor, have been known to provide cardiovascular and renal protection due effects on diuresis natriuresis. However, the natriuretic effect of SGLT2 inhibitors has reported be transient, long-term data related diuretic change are sparse. This study was performed assess 12-week treatment with empagliflozin (3 mg/kg) in diabetic OLETF rats by comparing it other antihyperglycemic agents including...

Prostaglandin (PG) A2, one of cyclopentenone PGs, is known to induce activation apoptosis in various cancer cells. Although PGA2 has been reported cause by altering the expression apoptosis-related genes, role p53, most critical pro-apoptotic on PGA2-induced not clarified yet. To address this issue, we compared HCT116 p53 null cells (HCT116 p53-/-) that containing wild type gene. Cell death induced was associated with phosphorylation histone H2A variant H2AX (H2AX), caspase-3 and cleavage...

Molecular mechanism of lung carcinogenesis and its aggressive nature is still largely elusive. To uncover the biomarkers related with tumorigenesis behavior cancer, we screened novel differentially expressed genes (DEG) in A549 cancer cell line by comparison CCD-25Lu, normal pulmonary epithelial line, using annealing control primer(ACP)-based GeneFishing system. Of DEGs, over-expression leucyl-tRNA synthetase 1 (LARS1) was prominent this up-regulation confirmed immunoblotting real-time...

Although the mechanism of cyclosporine A (CsA)‑induced renal injury remains to be fully elucidated, accumulating evidence suggests that oxidative stress is critical in producing CsA‑induced structural and functional impairment. The present study investigated effect D‑pinitol, a cyclitol soybean, on chronic CsA nephropathy. Male ICR mice were treated with vehicle, (30 mg/kg/day), D‑pinitol (50 mg/kg/day) or combination for 28 days. To assess which pathway responding augmented by expression...

We reported earlier that expression of Sox-4 was found to be elevated during prostaglandin (PG) A(2) and delta(12)-PGJ(2) induced apoptosis in human hepatocarcinoma Hep3B cells. In this study, the role examined using HepG2 cell lines. induction by several apoptotic inducer such as A23187 (Ca(2+) ionophore) etoposide (topoisomerase II inhibitor) transfection into cells were able induce observed cellular DNA fragmentation. Antisense oligonucleotide inhibited blocked formation fragmentation...

Nutlin-3 is a small-molecule antagonist of murine double minute 2 (MDM2) that blocks its binding to p53, leading an increase in p53 protein levels. The tumor suppressor induces growth arrest or apoptosis response genotoxic stress. Along with growth‑suppressive effect, it has been reported stimulates the mitogen-activated kinase (MAPK) pathway via upregulation heparin- epidermal factor-like factor (HB-EGF), receptor (EGFR) ligand, and discoidin domain 1 (DDR1), tyrosine receptor, at...

Background Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines oxidative stress could be involved disease-related renal injury, pathogenic link between metabolic derangement within cells injury remains unclear. Methods Renal fibrosis was triggered unilateral ureteral obstruction (UUO) mice with to investigate mechanism leading diseased kidneys....

The aim of this study was to assess any potential additive effects a treatment combining aliskiren with paricalcitol on reducing renal fibrosis. C57BL/6J mice were treated individually and/or until 7 days after initiation unilateral ureteral obstruction (UUO).In obstructed kidneys UUO mice, monotherapy or significantly attenuated interstitial fibrosis, collagen IV accumulation, and α-smooth muscle actin- terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling-positive cells....

Human hepatocarcinoma cells (SK‐HEP‐1) were induced to die through apoptosis by treatment with Δ 12 ‐prostaglandin (PG)J 2 , as characterized the appearance of a typical DNA ladder. The induction ‐PGJ was specifically blocked cycloheximide (CHX). Western analysis using anti‐p53 or anti‐WAF1 monoclonal antibodies demonstrated that these two protein levels increased 3 h after treatment, and accumulated for up h. p53 seemed be dependent on increase mRNA level, which inhibited CHX treatment....

Previous studies reported that high levels of nitric oxide (NO) induce apoptotic cell death in osteoblasts. We examined molecular mechanisms cytotoxic injury induced by sodium nitroprusside (SNP), a NO donor, both glutathione (GSH)-depleted and control U2-OS Cell viability was reduced much lower effective concentrations SNP GSH-depleted cells compared to normal cells. The data suggest the level intracellular GSH is critical SNP-induced processes oxidative stress due treatments doubled when...

Nutlin-3 which occupies the p53 binding pocket in HDM2, has been reported to activate apoptosis through both transcriptional activity-dependent and -independent programs of p53. Transcription-independent by nutlin-3 is triggered translocated mitochondria. However, we previously demonstrated that nutlin-3-induced mitochondrial translocation stimulates ERK1/2 activation, an anti-apoptosis signal, via ROS generation. We report on how nutlin-3-stimulated activity inhibits p53-induced apoptosis....

Prostaglandin (PG) A2, a cyclopentenone PG, induced apoptosis in both HCT116 and p53 -/- cells. Although PGA2-induced cells was dependent on the p53-DR5 pathway, mechanism underlying remains unknown. In this study, we observed that PGA2 caused an increase of mRNA expression DR5 protein even cells, accompanied by caspase-dependent apoptosis. Knockdown RNA interference inhibited Parallel to induction apoptosis, treatment upregulated genes upstream such as ATF4 CHOP. CHOP prevented...

Previously we reported that 3-deazaadenosine (DZA), a potent inhibitor and substrate forS-adenosylhomocysteine hydrolase inhibits bacterial lipopolysaccharide-induced transcription of tumor necrosis factor-α interleukin-1β in mouse macrophage RAW 264.7 cells. In this study, demonstrate the effects DZA on nuclear factor-κB (NF-κB) regulation. transcriptional activity NF-κB through hindrance p65 (Rel-A) phosphorylation without reduction its translocation DNA binding activity. The inhibitory...