Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ-p53-p21 signaling pathway.

Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that catalyzes hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. However, canonical and non-canonical functions of ACOT7 remain to be discovered. In this study, for the first time, ACOT7 was shown to be responsive to genotoxic stresses such as ionizing radiation (IR) and the anti-cancer drug doxorubicin in time- and dose-dependent manners.

Effect of extremely low frequency magnetic fields on cell proliferation and gene expression.

Owing to concerns regarding possible effects of extremely low frequency magnetic fields (ELF-MF) on human health, many studies have been conducted to elucidate whether ELF-MF can induce modifications in biological processes. Despite this, controversies regarding effects of ELF-MF are still rife. In this study, we investigated biological effects of ELF-MF on MCF10A, MCF7, Jurkat, and NIH3T3 cell lines.

Evaluation of premature senescence and senescence biomarkers in carcinoma cells and xenograft mice exposed to single or fractionated irradiation.

The purpose of the present study was to elucidate whether premature senescence contributes to the outcome of radiotherapy (RT) and to validate senescence biomarkers in vitro and in vivo. Cultured human cancer cell lines and xenografted mice were exposed to single (SR; 2, 6 or 12 Gy) or fractionated radiation (FR; 3 x 2 Gy or 6 x 2 Gy), and premature senescence was assessed using senescence-associated β-galactosidase (SA-β-Gal) activity, hypophosphorylation of pRb and p21 accumulation. A variety of senescence-associated biomarkers including cathepsin D (CD), the eukaryotic translation elongation factors eEF1A1, eEF1B2, decoy receptor 2 and Dec1 were further validated in vivo or in vitro.

Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment.

Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Here, we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA-induced silencing complex (RISC), with target p21 mRNA via binding of the stem-loop structure near the microRNA (miRNA) target site.

Secretome analysis of ionizing radiation-induced senescent cancer cells reveals that secreted RKIP plays a critical role in neighboring cell migration.

Cellular senescence is a physiological program of irreversible growth arrest that is considered to play an important role in tumor suppression. Recent studies demonstrated that senescent cells secrete multiple growth regulatory proteins that could alter the behavior of neighboring cells. In this study, we investigated the effect of secretory proteins from ionizing radiation (IR) induced senescent tumor cells on normal and tumor cells.

Effects of 837 and 1950 MHz radiofrequency radiation exposure alone or combined on oxidative stress in MCF10A cells.

The aim of this study was to determine whether the exposure to either single or multiple radio-frequency (RF) radiation frequencies could induce oxidative stress in cell cultures. Exposures of human MCF10A mammary epithelial cells to either a single frequency (837 MHz alone or 1950 MHz alone) or multiple frequencies (837 and 1950 MHz) were conducted at specific absorption rate (SAR) values of 4 W/kg for 2 h. During the exposure period, the temperature in the exposure chamber was maintained isothermally.

Effects of combined radiofrequency radiation exposure on the cell cycle and its regulatory proteins.

The aim of this study was to investigate whether single or combined radio frequency (RF) radiation exposure has effects on the cell cycle and its regulatory proteins. Exposure of MCF7 cells to either single (837 MHz) or combined (837 and 1950 MHz) RF radiation was conducted at specific absorption rate values of 4 W/kg for 1 h. During the exposure period, the chamber was made isothermal by circulating water through the cavity.

Time-dependently expressed markers and the characterization for premature senescence induced by ionizing radiation in MCF7.

Senescence has been suggested as a defense mechanism to block sporadic induction of cancer cells. Radiation treatment induces proliferating cancer cells to turn into non-proliferating senescent cells in vitro. To characterize transcriptional reprogramming after radiation treatment, we measured the gene expression profiles of MCF7 at different time points after treatment.

TIS21/(BTG2) negatively regulates estradiol-stimulated expansion of hematopoietic stem cells by derepressing Akt phosphorylation and inhibiting mTOR signal transduction.

It has been known that 12-O-tetradecanoyl phorbol-13-acetate-inducible sequence 21 (TIS21), ortholog of human B-cell translocation gene 2, regulates expansions of stage-specific thymocytes and hematopoietic progenitors. In the present study, lineage-negative (Lin(-))/stem cell antigen-1-positive (Sca-1+)/c-Kit+ (LSK) cell content was significantly elevated in bone marrow (BM) of TIS21-knockout (TIS21(-/-)) female mice, suggesting 17beta-estradiol (E(2))-regulated progenitor expansion. E(2) induced DNA synthesis and cell proliferation of mouse embryonic fibroblasts (MEFs) isolated from TIS21(-/-) mice, but not wild type (WT).

Lovastatin inhibits oxidized low-density lipoprotein-induced plasminogen activator inhibitor and transforming growth factor-beta1 expression via a decrease in Ras/extracellular signal-regulated kinase activity in mesangial cells.

Oxidized low-density lipoprotein (Ox-LDL) might be involved in the progression of renal disease. Ox-LDL stimulation of plasminogen activator inhibitor-1 (PAI-1) expression via transforming growth factor-beta (TGF-beta)/Smad signaling in mesangial cells required activation of extracellular signal-regulated kinase (ERK). Mevalonate depletion by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, decreases the levels of farnesyl pyrophosphate (FPP) for isoprenylation of Ras.

Role of CAGA boxes in the plasminogen activator inhibitor-1 promoter in mediating oxidized low-density lipoprotein-induced transcriptional activation in mesangial cells.

Oxidized low-density lipoprotein (Ox-LDL) activates transforming growth factor-beta (TGF-beta)/Smad signaling to stimulate plasminogen activator inhibitor-1 (PAI-1) expression in mesangial cells. Smad-binding sequences, termed CAGA boxes, are present in the promoter of human PAI-1 gene, and they mediate TGF-beta transcriptional induction. However, the functional role of each CAGA box in the Ox-LDL-induced PAI-1 promoter activation is unknown.

ERK contributes to the effects of Smad signaling on oxidized LDL-induced PAI-1 expression in human mesangial cells.

Oxidized low-density lipoprotein (Ox-LDL) stimulates plasminogen activator inhibitor-1 (PAI-1) expression in human mesangial cells mediated by transforming growth factor-beta (TGF-beta)/Smad signaling pathway. TGF-beta activates extracellular signal-regulated kinase (ERK) in mesangial cells, and ERK is involved in activation of Smad2/3. This study examines whether an interaction exists between Ox-LDL-induced TGF-beta/Smad signaling pathways and ERK activation leading to PAI-1 transcription in human mesangial cells.

Oxidized LDL activates PAI-1 transcription through autocrine activation of TGF-beta signaling in mesangial cells.

Background: Lipid abnormalities and oxidative stress may be involved in the development of glomerulosclerosis. Plasminogen activator inhibitor-1 (PAI-1) is a component of extracellular matrix (ECM) and target gene of transforming growth factor-beta (TGF-beta). Smad proteins play a key role in TGF-beta signaling, and Smad binding CAGA boxes are present in the PAI-1 promoter.

Heterozygous mice for TGF-betaIIR gene are resistant to the progression of streptozotocin-induced diabetic nephropathy.

Background: Transforming growth factor-beta (TGF-beta) receptor complex and its downstream Smad signaling intermediates constitute an extracellular matrix (ECM) accumulation pathway.

Methods: In the present study, we examined whether decreased expression of the TGF-beta type II receptor (TGF-betaIIR) in TGF-betaIIR gene heterozygous (TGF-betaIIR+/-) (HT) mice could inhibit the Smad signaling pathway and subsequent progression of renal lesions when streptozotocin (STZ) diabetes is induced.

Results: At the end of the 28-week experiment after STZ injections, wild-type diabetic mice showed severe glomerular hypertrophy and mesangial matrix accumulation occasionally featuring nodular glomerulosclerosis.

Glycated albumin induces superoxide generation in mesangial cells.

Background/aims: Reactive oxygen species are involved in the pathogenesis of diabetic nephropathy. Amadori-modified glycated albumin modulates signaling pathways in mesangial cells that contribute to the development of diabetic nephropathy. However, the effects of glycated albumin on mesangial cell superoxide (O2-) production are unknown.

Glycated albumin activates PAI-1 transcription through Smad DNA binding sites in mesangial cells.

Amadori-modified glycated albumin stimulates extracellular matrix and transforming growth factor-beta (TGF-beta) expression in cultured mesangial cells. Smad proteins transduce the TGF-beta-mediated signal, and Smad-binding CAGA sequences are present in the plasminogen activator inhibitor-1 (PAI-1) promoter. This study examined whether glycated albumin induces PAI-1 transcription in human mesangial cells (HMC) through Smad-binding sites in the PAI-1 promoter.

Angiotensin II mediates LDL-induced superoxide generation in mesangial cells.

Lipid abnormalities and activation of the local renin-angiotensin system (RAS) may be involved in the pathogenesis of chronic glomerular disease. This study investigated whether low-density lipoprotein (LDL) activates local RAS in cultured human mesangial cells (HMC) and, at the same time, whether ANG II mediates LDL-induced mesangial cell proliferation, hypertrophy, and superoxide (O2-) generation. Quiescent HMC were exposed to 50 to 200 microg/ml of LDL or 10-7 to 10-10 M ANG II for 0.

Biphasic regulation of plasminogen activator/inhibitor by LDL in mesangial cells.

Lipid abnormalities and dysregulation of the plasminogen activator (PA)/plasmin system may be involved in the development of glomerulosclerosis. We investigated the effects of low-density lipoprotein (LDL) on PA inhibitor-1 (PAI-1), urokinase-type PA (uPA), and tissue-type PA (tPA) in relationship to protein kinase C (PKC) in cultured human mesangial cells (HMC). LDL (200 microg/ml) induced two peaks of PKC activation at hours 0.