scholarly journals Modulation of p21, DAPK1 and COX-2 during the DMBA/TPA-induced mouse skin tumorigenesis and its prevention by phytic acid

2014 ◽  
Vol 2 (04) ◽  
pp. 61-67
Author(s):  
Chhaya Pandey ◽  
Rashmi Arnold ◽  
Rahasya Mani Mishra
Keyword(s):  
Phytic Acid ◽  
Methylation Status ◽  
Mouse Skin ◽  
Experimental Models ◽  
Time Dependent ◽  
Dependent Manner ◽  
Protective Effects ◽  
Skin Tumorigenesis ◽  
Naturally Occurring ◽  
Cox 2

Chemoprevention by naturally occurring agents is gaining much attention as a newer dimension in the management of cancer. Many naturally occurring agents have shown cancer chemopreventive potential in a variety of bioassay systems and animal models, having relevance to human disease. Phytic acid or Inositol hexaphosphate (IP6), an antioxidant, is a naturally occurring polyphosphorylated carbohydrate that has shown a strong anticancer activity in several experimental models. We assessed the protective effects of Phytic acid against the 7, 12-dimethylbenz [a] anthracene (DMBA)/ 12-O-tetradecanoylphorbol-13- acetate (TPA) induced mouse skin tumorigenesis at 4 and 16 weeks, the time before and after the tumor development. At molecular level we studied expression and promoter CpG methylation status of p21, DAPK1 and COX-2. Our data suggests exposure of DMBA/TPA methylated the promoter region of p21 and DAPK1 genes in time dependent manner that could be the cause of down regulation of their expression with time, which were reversed by administration of phytic acid. But we did not observe methylation in COX-2 whereas upregulation of COX-2 was observed at protein level in mice treated with DMBA followed by TPA in time dependent manner. Administration of phytic acid prevented theses DMBA/TPA induced molecular changes. Study provides a rationale for cancer chemoprevention by natural occurring compounds like Phytic acid.

Protective effect of the dimer of 16,16-diMePGB1 against KCN-induced mitochondrial failure in hepatocytes

1992 ◽  
Vol 263 (2) ◽  
pp. C405-C411 ◽  
Author(s):  
Y. Park ◽  
T. M. Devlin ◽  
D. P. Jones
Keyword(s):  
Membrane Potential ◽  
Protective Effect ◽  
Ion Transport ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Time Dependent ◽  
Dependent Manner ◽  
Protective Effects ◽  
Cellular Swelling

The dimer and trimer of 16,16-dimethyl-15-dehydroprostaglandin B1 (16,16-diMePGB1) previously have been shown to have protective effects on mitochondrial function. To examine the potential mechanisms involved in protection against mitochondrial failure, we have studied the effects of the dimer of 16,16-diMe-PGB1 (dicalciphor) on mitochondrial function in hepatocytes exposed to KCN. Addition of micromolar concentrations of dicalciphor provided substantial protection against KCN-induced toxicity in a concentration- and time-dependent manner. Dicalciphor, however, had no effect on total or mitochondrial ATP losses in KCN-treated cells. The dimer prevented the marked loss of mitochondrial membrane potential (delta psi) and delta pH that occurs as a result of KCN treatment and prevented KCN-induced loading of phosphate in mitochondria. Furthermore, the dimer of 16,16-diMePGB1 also prevented KCN-induced mitochondrial and cellular swelling. These results demonstrate that dicalciphor protects against KCN-induced damage and that this protection is associated with regulation of specific mitochondrial ion transport functions.

scholarly journals The Metabolic Chemical Reporter Ac46AzGal Could Incorporate Intracellular Protein Modification in the Form of UDP-6AzGlc Mediated by OGT and Enzymes in the Leloir Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Jiajia Wang ◽  
Biao Dou ◽  
Lu Zheng ◽  
Wei Cao ◽  
Peiyu Dong ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Protein Modification ◽  
Time Dependent ◽  
Dependent Manner ◽  
Intracellular Protein ◽  
Galactose Metabolism ◽  
Naturally Occurring ◽  
Leloir Pathway ◽  
Chemical Reporter ◽  
Complex Glycans

Galactose is a naturally occurring monosaccharide used to build complex glycans that has not been targeted for labeling as a metabolic reporter. Here, we characterize the cellular modification of proteins by using Ac46AzGal in a dose- and time-dependent manner. It is noted that a vast majority of this labeling of Ac46AzGal occurs intracellularly in a range of mammalian cells. We also provided evidence that this labeling is dependent on not only the enzymes of OGT responsible for O-GlcNAcylation but also the enzymes of GALT and GALE in the Leloir pathway. Notably, we discover that Ac46AzGal is not the direct substrate of OGT, and the labeling results may attribute to UDP-6AzGlc after epimerization of UDP-6AzGal via GALE. Together, these discoveries support the conclusion that Ac46AzGal as an analogue of galactose could metabolically label intracellular O-glycosylation modification, raising the possibility of characterization with impaired functions of the galactose metabolism in the Leloir pathway under certain conditions, such as galactosemias.

scholarly journals Colon distention induces persistent visceral hypersensitivity by mechanotranscription of pain mediators in colonic smooth muscle cells

2015 ◽  
Vol 308 (5) ◽  
pp. G434-G441 ◽  
Author(s):  
You-Min Lin ◽  
Yu Fu ◽  
Chester C. Wu ◽  
Guang-Yin Xu ◽  
Li-Yen Huang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Pain ◽  
Smooth Muscle Cells ◽  
Mechanical Stress ◽  
Muscle Cells ◽  
Visceral Hypersensitivity ◽  
Time Dependent ◽  
Rat Colon ◽  
Dependent Manner ◽  
Cox 2

Abdominal pain and distention are major complaints in irritable bowel syndrome. Abdominal distention is mainly attributed to intraluminal retention of gas or solid contents, which may cause mechanical stress to the gut wall. Visceral hypersensitivity (VHS) may account for abdominal pain. We sought to determine whether tonic colon distention causes persistent VHS and if so whether mechanical stress-induced expression (mechanotranscription) of pain mediators in colonic smooth muscle cells (SMCs) plays a role in VHS. Human colonic SMCs were isolated and stretched in vitro to investigate whether mechanical stress upregulates expression of the pain mediator cyclooxygenase-2 (COX-2). Rat colon was distended with a 5-cm-long balloon, and gene expression of COX-2, visceromotor response (VMR), and sensory neuron excitability were determined. Static stretch of colonic SMCs induced marked expression of COX-2 mRNA and protein in a force- and time-dependent manner. Subnoxious tonic distention of the distal colon at ∼30–40 mmHg for 20 or 40 min induced COX-2 expression and PGE2 production in colonic smooth muscle, but not in the mucosa layer. Lumen distention also increased VMR in a force- and time-dependent manner. The increase of VMR persisted for at least 3 days. Patch-clamp experiments showed that the excitability of colon projecting sensory neurons in the dorsal root ganglia was markedly augmented, 24 h after lumen distention. Administration of COX-2 inhibitor NS-398 partially but significantly attenuated distention-induced VHS. In conclusion, tonic lumen distention upregulates expression of COX-2 in colonic SMC, and COX-2 contributes to persistent VHS.

scholarly journals Promoting effect of Se-allylselenocysteine on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis

2020 ◽  
Vol 9 ◽  
Author(s):  
An-Chin Cheng ◽  
Wan-Ru Jiang ◽  
Yu-Hsuan Hsiao ◽  
Vladimir Badmaev ◽  
Chi-Tang Ho ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Positive Control ◽  
Positive Control Group ◽  
Raw 264.7 Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Promoting Effect ◽  
Skin Tumorigenesis ◽  
Cox 2 ◽  
Anti Inflammatory

Se-allylselenocysteine (ASC), an analogue of garlic compound, has been shown to inhibit mammary carcinogenesis in vivo and cell growth in vitro. However, the function of ASC on anti-inflammatory effects remains largely unknown. Therefore, we investigated whether ASC has an anti-inflammatory effect on lipopolysaccharide (LPS) -induced inflammation or an anti-tumour effect promoting on DMBA/TPA-induced skin tumorigenesis and tried to elucidate the mechanisms involved. Herein, the results showed that ASC inhibited LPS-induced production of nitric oxide (NO) with a decreased protein level of inducible nitric oxide synthase (iNOS) in RAW 264.7 cells. However, ASC enhanced LPS-induced cyclooxygenase-2 (COX-2) protein levels and mRNA expression. Interestingly, we found for the first time that topical application of ASC on the dorsal skin of DMBA-initiated and TPA-promoted mice significantly accelerated skin tumorigenesis and raised tumour multiplicity as compared to the positive control group (DMBA/TPA). The number of tumours that were 1–3 mm, 3–5 mm, and >5 mm in size per mouse increased in a dose-dependent manner in the ASC pre-treated groups. Pre-treatment with ASC showed a significant increase in the expression of COX-2 compared with the positive control group. In summary, that ASC may modulate the COX-2 protein expression and promoting DMBA/TPA-induced skin cancer in mice.

Effects of Celecoxib on Human Acute Promyelocytic Leukemia Cell Line and Its Mechanism.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2851-2851
Author(s):  
Yun Xu ◽  
He Huang ◽  
Yanmin Zhao ◽  
Fenfang Zeng ◽  
Qian Zhou
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Fusion Gene ◽  
Telomerase Activity ◽  
Promyelocytic Leukemia ◽  
Time Dependent ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Cycle Arrest ◽  
Cox 2

Abstract Acute promyelocytic leukemia (APL) is a special subtype of acute myelogenous leukemia (AML) which is characterized for a specific translocation between chromosome 15 and 17 [t(15;17)] and the expression of PML/RARα fusion gene. Celecoxib, one of the specific inhibitors of cyclooxygenase-2 (COX-2), has been reported to induce anti-neoplastic activity on many solid human tumor cell lines in recent years. In our study, ATRA resistant APL cell line MR2 cells were used to investigate the effects of celecoxib on hematological malignancy. MR2 cells were treated with celecoxib at different concentration (0, 20, 40, 80, 120 and 160μmol/L). The proliferation of MR2 cells was observed by MTT assay and apoptosis was detected by DNA fragmentation analysis and flow cytometry using Annexin V-FITC/PI staining. Western blot was used to detect the change of caspase-8, -9, -3 and PARP in MR2 cells. The expression of mRNA of fusion gene PML/RARα, COX-2 and survivin, bcl-2/bax, CIAP1 and CIAP2 was assessed by reverse transcription polymerase chain reaction (RT-PCR). Cell cycle analyzed by flow cytometry with PI staining and western blot was used to detect the expression of cell-cycle-regulating proteins. The telomerase activity of MR2 cells was analyzed by PCR-ELISA. The expression of hTERT mRNA and c-myc mRNA was assessed by RT-PCR. MR2 cells viability in presence of celecoxib decreased markedly in a dose- and time- dependent manner. After treated with celecoxib (20-160μmol/L) for 12-48h, the proliferation of MR2 cells were inhibited significantly, in comparison with the control group (P<0.01). 50% growth inhibition (IC50) at 24h and 48h was 80.93μmol/L and 71.72μmol/L, respectively. A DNA ladder pattern of internucleosomal fragmentation was observed. The translocation of phosphatidylserine at the outer surface of the cell plasma membrane could be induced by celecoxib and its level increased following the augmentation of the drug concentration. MR2 cells exposure to 40-160μmol/L celecoxib for 24h caused 9.59%, 24.00%, 36.10% apoptotic cells, which was more than that of the untreated group 2.84% (P<0.01). The expression of survivin mRNA decreased dramatically, while no significant change with PML/RARα and COX-2. Treatment with celecoxib for 24h resulted in the activation of caspase-3 and caspase-9, cleavage of PARP. 40-160μmol/L celecoxib led to cell cycle arrest in G1/S phase, and CyclinD1 and CyclinE decreased, accompanied with up-regulation of P21waf/cip1, P27KIP, P16INK4a. celecoxib could inhibit the telomerase activity of APL cell line, and the inhibition was dose- and time- dependent. The expression of hTERT mRNA and c-myc mRNA were down-regulated by celecoxib in dose- dependent manner. These results indicated that celecoxib could inhibit MR2 cells proliferation by inducing apoptosis, cell cycle arrest and suppression of telomerase activity.

Oroxylin A Shows Protective Effects on Biological Activity of Lipopolysaccharide Treated Human Periodontal Ligament Stem Cells

2019 ◽  
Vol 9 (10) ◽  
pp. 1362-1368
Author(s):  
Ting Wang ◽  
Xinqiang Liu ◽  
Chunmiao Jiang ◽  
Dapeng Ren ◽  
Yuli Gao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Biological Activity ◽  
Periodontal Ligament ◽  
Time Dependent ◽  
Dependent Manner ◽  
Protective Effects ◽  
Oroxylin A ◽  
Periodontal Ligament Stem Cells ◽  
Dose Dependent

The abnormal proliferation and apoptosis of human periodontal ligament stem cells (hPDLSCs) serves a crucial role in the development of periodontitis. Oroxylin A has shown protective effects in a variety of inflammatory diseases. The present study was aimed to investigate the effects of oroxylin A on lipopolysaccharide (LPS) treated hPDLSCs. In the present study, cells were exposed to different concentrations (10, 20, 40 uM) of oroxylin A for 24 h or 48 h, co-treated with LPS. The cell proliferation capacity was assessed using cell counting kit-8 (CCK-8), and the cell apoptosis was evaluated by flow cytometry. The Ki67 expression was measured using immunofluorescence and NO production was detected by enzyme linked immunosorbent assay (ELISA) respectively. Western blot analyses were used to investigate the level of cell proliferation related proteins (PCNA, CDK2 and p21) as well as NF-κB, I-κBα and downstream molecules iNOS, IL-6 and TNF-α. The results demonstrated that oroxylin A increased cell survival of LPS treated hPDLSCs in a dose-dependent and time-dependent manner. In addition, oroxylin A treatment inhibited cell apoptosis in hPDLSCs. Furthermore, the levels of NO, NF-κB, iNOS, IL-6 and TNF-α were significantly reduced. And the expression of Ki67, I-κBα, PCNA and CDK2 were significantly increased. Taken together, these findings indicate that oroxylin A promote proliferation and suppress apoptosis in a dose-dependent and time-dependent manner. Oroxylin A may affects LPS induced biological activity via inhibiting NF-κB activation and proinflammatory cytokines expression in hPDLSCs.

scholarly journals Protective Effects of Sesamin Against UVB-Induced Skin Inflammation and Photodamage In Vitro and In Vivo

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 479 ◽  
Author(s):  
Lin ◽  
Wu ◽  
Hou ◽  
Chien ◽  
Chang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Map Kinase ◽  
Human Fibroblasts ◽  
Mouse Skin ◽  
P38 Map Kinase ◽  
Dermal Fibroblasts ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Protective Effects ◽  
Cox 2

Ultraviolet (UV) exposure has been demonstrated as the most critical factor causing extrinsic skin aging and inflammation. This study explored the protective effects and mechanisms of sesamin against skin photodamage. Sesamin reduced intracellular reactive oxygen species production after UVB irradiation in human dermal fibroblasts. The sesamin treatment attenuated mitogen-activated protein (MAP) kinase phosphorylation and matrix metalloproteinase (MMPs) overexpression induced by UVB exposure, and it significantly enhanced the tissue inhibitor of metalloproteinase-1 protein expression. Sesamin also elevated the total collagen content in human fibroblasts by inhibiting UVB-induced mothers against decapentaplegic homolog 7 (Smad7) protein expression. Sesamin reduced UVB-induced inducible nitric oxide synthase (i-NOS) and cyclooxygenase-2 (COX-2) overexpression and inhibited nuclear factor-kappa B (NF-κB) translocation. Moreover, sesamin may regulate the c-Jun N-terminal kinases (JNK) and p38 MAP kinase pathways, which inhibit COX-2 expression. Sesamin could reduce UVB-induced inflammation, epidermal hyperplasia, collagen degradation, and wrinkle formation in hairless mice. It also reduced MMP-1, interleukin (IL-1), i-NOS, and NF-κB in the mouse skin. These results demonstrate that sesamin had antiphotodamage and anti-inflammatory activities. Sesamin has potential for use as a skin protection agent in antiphotodamage and skin care products.

Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals

1989 ◽  
Vol 257 (3) ◽  
pp. H804-H811 ◽  
Author(s):  
M. Kaneko ◽  
V. Elimban ◽  
N. S. Dhalla
Keyword(s):  
Free Radicals ◽  
Oxygen Free Radicals ◽  
Sulfhydryl Group ◽  
Sulfhydryl Groups ◽  
Time Dependent ◽  
Dependent Manner ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Sulfhydryl Reagents ◽  
Dose Dependent

To understand the involvement of changes in sulfhydryl groups in causing depression of the sarcolemmal Ca2+-pump activities, this study was undertaken to examine the effects of oxygen free radicals on rat heart sarcolemmal sulfhydryl groups, Ca2+-stimulated adenosinetriphosphatase (ATPase), and ATP-dependent Ca2+ accumulation. In addition, the effects of sulfhydryl reagents such as dithiothreitol, cysteine, and N-ethylmaleimide on Ca2+-pump activities were investigated. The inhibition of sarcolemmal Ca2+-pump activities by O2-. (xanthine + xanthine oxidase) and H2O2 was decreased by the addition of dithiothreitol or cysteine in a dose-dependent manner. N-ethylmaleimide also showed inhibitory effects on Ca2+-pump activities both in a dose- and time-dependent manner; dithiothreitol and cysteine prevented changes in Ca2+-pump activities because of N-ethylmaleimide. Heart sarcolemmal sulfhydryl groups were depressed by O2-., H2O2, and .OH (H2O2 + Fe2+) both in a dose- and time-dependent manner. Superoxide dismutase, catalase, and D-mannitol showed protective effects on the sulfhydryl group depression by O2-., H2O2, and .OH, respectively. A significant correlation between changes in sarcolemmal Ca2+-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen. These results indicate that oxygen free radicals may depress the heart sarcolemmal Ca2+-pump activities by modifying the sulfhydryl groups in the sarcolemmal membrane.

scholarly journals Estrogen Inhibits Bone Resorption by Directly Inducing Apoptosis of the Bone-resorbing Osteoclasts

1997 ◽  
Vol 186 (4) ◽  
pp. 489-495 ◽  
Author(s):  
Takashi Kameda ◽  
Hiroshi Mano ◽  
Tatsuhisa Yuasa ◽  
Yoshihisa Mori ◽  
Koshi Miyazawa ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Estrogen Replacement Therapy ◽  
Time Dependent ◽  
Osteoclastic Bone Resorption ◽  
Dependent Manner ◽  
Protective Effects ◽  
Estrogen Replacement ◽  
Induction Of Apoptosis ◽  
Direct Induction ◽  
Osteoclast Apoptosis

Estrogen deficiency causes bone loss, which can be prevented by estrogen replacement therapy. Using a recently developed technique for isolation of highly purified mammalian osteoclasts, we showed that 17 β-estradiol (E2) was able to directly inhibit osteoclastic bone resorption. At concentrations effective for inhibiting bone resorption, E2 also directly induced osteoclast apoptosis in a dose- and time-dependent manner. ICI164,384 and tamoxifen, as pure and partial antagonists, respectively, completely or partially blocked the effect of E2 on both inhibition of osteoclastic bone resorption and induction of osteoclast apoptosis. These data suggest that the protective effects of estrogen against postmenopausal osteoporosis are mediated in part by the direct induction of apoptosis of the bone-resorbing osteoclasts by an estrogen receptor– mediated mechanism.

scholarly journals Characteristics of resveratrol and serotonin on antioxidant capacity and susceptibility to oxidation of red blood cells in stored human blood in a time-dependent manner

2017 ◽  
Vol 46 (1) ◽  
pp. 272-283 ◽  
Author(s):  
Zübeyir Huyut ◽  
Mehmet Ramazan Şekeroğlu ◽  
Ragıp Balahoroğlu ◽  
Mehmet Tahir Huyut
Keyword(s):  
Antioxidant Capacity ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Time Dependent ◽  
Dependent Manner ◽  
Protective Effects ◽  
Activity Time ◽  
Citrate Phosphate Dextrose ◽  
Citrate Phosphate ◽  
Over Time

Objective In stored red blood cells (RBCs), which are used in diseases (e.g., acute blood loss and leukaemia), storage lesions arise by oxidative stress and other factors over time. This study investigated the protective effects of resveratrol and serotonin on stored RBCs. Methods Blood from each donor (n = 10) was placed in different bags containing 70 mL of citrate phosphate dextrose (total volume: 500 mL) and divided into three groups (n = 30): control, 60 µg/mL resveratrol, and 60 µg/mL serotonin. Malondialdehyde (MDA) and glutathione (GSH) levels, activity of glutathione peroxidase (GSH-Px), catalase, and carbonic anhydrase (CA), and susceptibility to oxidation in RBCs, and pH in whole blood were measured at baseline and on days 7, 14, 21, and 28. Results MDA levels and susceptibility to oxidation were increased in all three groups time-dependently, but this increase was greater in the serotonin group than in the other groups. Activity of GSH-Px, CAT, and CA, as well as GSH levels, were decreased in the control and serotonin groups time-dependently, but were significantly preserved in the resveratrol group. The pH was decreased in all groups time-dependently. Conclusion Our study shows that resveratrol attenuates susceptibility to oxidation of RBCs and protects their antioxidant capacity, and partially preserves CA activity time-dependently.

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