Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
Add more filters










Database
Language
Publication year range
1.
Kaohsiung J Med Sci ; 35(6): 332-340, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30903681

ABSTRACT

Chemokine-like factor (CKLF)-like, MAL and related proteins for vesicle trafficking and membrane link (MARVEL) transmembrane domain-containing family proteins (CMTMs) have significant roles in the immune system, in male reproduction, as well as in tumorigenesis. Previous studies have shown that CMTM family member 7 (CMTM7) was broadly expressed in various normal tissues, but not in lung, gastric, esophageal, pancreas, and cervix cancers. To explore its relationship with liver cancer, we examined the expression of CMTM7 in liver cancers and its correlation with clinical and pathological conditions. We found that CMTM7 expression was markedly reduced in liver cancer tissues, and negatively correlated with TNM staging and tumor metastasis. In vitro studies showed that enforced expression of CMTM7 inhibited the cell growth and migration of liver cancer cells. Further analysis revealed that CMTM7 suppressed AKT signaling and induced cell cycle arrest at the G0/G1 phase in the liver cancer cells, likely as the consequent of decreased levels of cyclin D1, cyclin-dependent kinase 4 (CDK4), and CDK6, and increased p27 expression. Thus, CMTM7 functions as a tumor suppressor in liver cancer through suppressing cell cycle progression.


Subject(s)
Carcinogenesis/genetics , Carcinoma, Hepatocellular/genetics , Chemokines/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , MARVEL Domain-Containing Proteins/genetics , Aged , Carcinogenesis/metabolism , Carcinogenesis/pathology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Cell Line, Tumor , Cell Proliferation , Chemokines/metabolism , Cyclin D1/genetics , Cyclin D1/metabolism , Cyclin-Dependent Kinase 4/genetics , Cyclin-Dependent Kinase 4/metabolism , Cyclin-Dependent Kinase 6/genetics , Cyclin-Dependent Kinase 6/metabolism , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Humans , Liver Cirrhosis/genetics , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/surgery , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Lymphatic Metastasis , MARVEL Domain-Containing Proteins/metabolism , Male , Middle Aged , Neoplasm Staging , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Resting Phase, Cell Cycle/genetics , Signal Transduction
2.
Int J Mol Sci ; 20(4)2019 Feb 23.
Article in English | MEDLINE | ID: mdl-30813425

ABSTRACT

Kaempferol (Kae) is a natural flavonoid with potent antioxidant activity, but its therapeutic use is limited by its low aqueous solubility. Here, a series of Kae derivatives were synthesized to improve Kae dissolution property in water and antioxidant activity. These compounds included sulfonated Kae (Kae-SO3), gallium (Ga) complexes with Kae (Kae-Ga) and Kae-SO3 (Kae-SO3-Ga). The compound structures were characterized by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy and thermal methods (TG/DSC). The results showed that a sulfonic group (-SO3) was successfully tethered on the C3' of Kae to form Kae-SO3. And in the metal complexation, 4-CO and 3-OH of the ligand participated in the coordination with Ga(III). The metal-to-ligand ratio 1:2 was suggested for both complexes. Interestingly, Kae-SO3-Ga was obviously superior to other compounds in terms of overcoming the poor water-solubility of free Kae, and the solubility of Kae-SO3-Ga was about 300-fold higher than that of Kae-Ga. Furthermore, the evaluation of antioxidant activities in vitro was carried out for Kae derivatives by using α,α-diphenyl-ß-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) free radical scavenging. The results showed that Kae-SO3-Ga was also optimal for scavenging free radicals in a dose-dependent manner. These data demonstrate that sulfonate kaempferol-gallium complex has a promising future as a potential antioxidant and as a potential therapeutic agent for further biomedical studies.


Subject(s)
Antioxidants/pharmacology , Free Radical Scavengers/pharmacology , Kaempferols/chemical synthesis , Kaempferols/pharmacology , Water/chemistry , Biphenyl Compounds/chemistry , Calorimetry, Differential Scanning , Carbon-13 Magnetic Resonance Spectroscopy , Mass Spectrometry , Picrates/chemistry , Proton Magnetic Resonance Spectroscopy , Solubility , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Sulfonic Acids/chemistry , Temperature , Thermogravimetry
3.
Exp Mol Med ; 50(3): e463, 2018 03 30.
Article in English | MEDLINE | ID: mdl-29869624

ABSTRACT

Gender differences in fatigue manifest as females being more prone to feel exhaustion and having lower muscle endurance. However, the mechanisms of these effects remain unclear. We investigated whether orosomucoid, an endogenous anti-fatigue protein that enhances muscle endurance, is involved in this regulation. Female rats exhibited lower muscle endurance, and this gender difference disappeared in orosomucoid-1-deficient mice. Female rats also exhibited weaker orosomucoid induction in serum, liver and muscle in response to fatigue compared with male rats. Ovariectomy elevated orosomucoid levels and increased swimming time, and estrogen replenishment reversed these effects. Exogenous estrogen treatment in male and female mice produced opposite effects. Estrogen decreased orosomucoid expression and its promoter activity in C2C12 muscle and Chang liver cells in vitro, and estrogen receptor or p38 mitogen-activated protein kinase blockade abolished this effect. Therefore, estrogen negatively regulates orosomucoid expression that is responsible for the weaker muscle endurance in females.


Subject(s)
Estrogens/pharmacology , Orosomucoid/metabolism , Receptors, Estrogen/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Blotting, Western , Cell Line , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle Fatigue/drug effects , Muscle Strength/drug effects , Ovariectomy , Physical Endurance/drug effects , Rats , Rats, Sprague-Dawley , Sex Factors
4.
Cell Res ; 23(11): 1270-83, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23979021

ABSTRACT

The vagus nerve can control inflammatory response through a 'cholinergic anti-inflammatory pathway', which is mediated by the α7-nicotinic acetylcholine receptor (α7nAChR) on macrophages. However, the intracellular mechanisms that link α7nAChR activation and pro-inflammatory cytokine production remain not well understood. In this study, we found that miR-124 is upregulated by cholinergic agonists in LPS-exposed cells and mice. Utilizing miR-124 mimic and siRNA knockdown, we demonstrated that miR-124 is a critical mediator for the cholinergic anti-inflammatory action. Furthermore, our data indicated that miR-124 modulates LPS-induced cytokine production by targeting signal transducer and activator of transcription 3 (STAT3) to decrease IL-6 production and TNF-α converting enzyme (TACE) to reduce TNF-α release. These results also indicate that miR-124 is a potential therapeutic target for the treatment of inflammatory diseases.


Subject(s)
Cholinergic Neurons/metabolism , Cytokines/biosynthesis , MicroRNAs/metabolism , ADAM Proteins/metabolism , ADAM17 Protein , Animals , Cells, Cultured , Cytokines/genetics , Cytokines/metabolism , HEK293 Cells , Humans , Interleukin-6/biosynthesis , Interleukin-6/genetics , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , STAT3 Transcription Factor/metabolism , Sepsis/chemically induced , Sepsis/genetics , Sepsis/metabolism , Sepsis/pathology , Transcription, Genetic , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/genetics , alpha7 Nicotinic Acetylcholine Receptor/metabolism
5.
Mol Biol Rep ; 39(2): 857-64, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21567198

ABSTRACT

Influenza A viruses expose two major surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Although N-glycosylation is essential for many glycoproteins, the glycoproteins expressed in yeast are sometimes hyper-glycosylated, which maybe a primary hindrance to the exploitation of therapeutic glycoprotein production because glycoproteins decorated with yeast-specific glycans are immunogenic and show poor pharmacokinetic properties in humans. To elucidate the NA with different glycosylation in interaction with immunogenicity, here we reported the heterologous expression of influenza NA glycoprotein derived from influenza virus A/newCaledonia/20/99(H1N1) in wide-type Pichia pastoris, α-1,6-mannosyltransferase (och1)-defective P. pastoris and Escherichia coli. We also assessed the immunogenicity of hyper-glycosylated NA expressed in the wide-type, low-glycosylated NA expressed in och1-defective P. pastoris strain and non-glycosylated NA produced in E. coli. Recombinant NA was expressed in wide-type P. pastoris as a 59-97 above kDa glycoprotein, 52-57 kDa in the och1 defective strain, and as a 45 kDa non-glycoprotein in E. coli. The antibody titers of Balb/c mice were tested after the mice were immunized three times with 0.2, 1, or 3 µg purified recombinant NA. Our results demonstrated that after the second immunization, the antibody titer elicited with 1 µg low-glycosylated NA was 1:5,500, while it was 1:10 and 1:13 when elicited by 1 µg hyper-glycosylated and non-glycosylated NA. In the 0.2 µg dose groups, a high antibody titer (1:4,900) was only found after third immunization by low-glycosylated NA, respectively. These results suggest that low-glycosylation in och1-defective P. pastoris enhances the immunogenicity of recombinant NA and elicits similar antibody titers with less antigen when compared with hyper- and non-glycosylated NA. Thus, och1-defective P. pastoris may be a better yeast expression system for production of glycoproteins to research immunogenic characterization.


Subject(s)
Bioreactors , Influenza A Virus, H1N1 Subtype/enzymology , Influenza Vaccines/immunology , Membrane Glycoproteins/immunology , Neuraminidase/metabolism , Pichia/metabolism , Recombinant Proteins/metabolism , Animals , Antibodies, Viral/blood , Blotting, Western , DNA Primers/genetics , Escherichia coli , Glycosylation , Influenza A Virus, H1N1 Subtype/genetics , Influenza Vaccines/metabolism , Mannosyltransferases/genetics , Mice , Mice, Inbred BALB C , Neuraminidase/genetics , Neuraminidase/immunology , Pichia/enzymology , Recombinant Proteins/genetics , Recombinant Proteins/immunology
6.
Acta Pharmacol Sin ; 32(2): 194-200, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21293472

ABSTRACT

AIM: To investigate the role of ATP-sensitive potassium (K(ATP)) channels on blood pressure variability (BPV) in sinoaortic denervated (SAD) rats. METHODS: SAD was performed on male Sprague-Dawley rats 4 weeks before the study. mRNA expression of Kir6.1, Kir6.2 and SUR2 in aorta and mesenteric artery was determined using real-time quantitative polymerase chain reaction, and confirmed at the protein level using Western blotting and laser confocal immunofluorescence assays. Concentration-response curves of isolated aortic and mesenteric arterial rings to adenosine and pinacidil were established. Effects of K(ATP) channel openers and blocker on BPV were examined in conscious SAD rats. RESULTS: Aortic SUR2 expression was significantly greater, while Kir6.1 was lower, in SAD rats than in sham-operated controls. In contrast, in the mesenteric artery both SUR2 and Kir6.1 expression were markedly lower in SAD rats than controls. For both arteries, Kir6.2 expression was indistinguishable between sham-operated and SAD rats. These findings were confirmed at the protein level. Responses of the aorta to both adenosine and pinacidil were enhanced after SAD, while the mesenteric response to adenosine was attenuated. Pinacidil, diazoxide, nicorandil, and glibenclamide significantly decreased BPV. CONCLUSION: These findings indicate that expression of vascular K(ATP) channels is altered by chronic SAD. These alterations influence vascular reactivity, and may play a role in the increased BPV in chronic SAD rats.


Subject(s)
Blood Pressure/physiology , KATP Channels/metabolism , RNA, Messenger/metabolism , Adenosine/administration & dosage , Adenosine/pharmacology , Animals , Aorta/drug effects , Aorta/injuries , Aorta/metabolism , Autonomic Denervation , Blood Pressure/drug effects , Blotting, Western , Carotid Sinus/innervation , Dose-Response Relationship, Drug , Male , Mesenteric Arteries/drug effects , Mesenteric Arteries/metabolism , Pinacidil/administration & dosage , Pinacidil/pharmacology , Polymerase Chain Reaction , Rats , Rats, Sprague-Dawley , Vasodilator Agents/administration & dosage , Vasodilator Agents/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...