1.Effects of different dietary fatty acid on expression of nuclear receptor genes in breast cancer of rats.
Na WEI ; Man-tian MI ; Bin WANG ; Jun-dong ZHU ; Da-peng ZHU ; Jia-lin YUAN
Chinese Journal of Preventive Medicine 2007;41(4):271-276
OBJECTIVETo study the effects of different dietary fatty acid on the expression of nuclear receptor genes in the breast cancer of rats.
METHODSFifty-day-old female Sprague-Dawley rats were fed on eight different diets containing following fatty acids: saturated fatty acid (SFA); monounsaturated fatty acid (MUFA); n-6 polyunsaturated fatty acid (PUFA); n-3 PUFA; 1:1 n-6/n-3; 5:1 n-6/n-3; 10:1 n-6/n-3; 1:2:1 S/M/P (n-6/n-3 at 1:1). The rats were given a single intraperitoneal injection of methyl-nitrosourea (MNU) at 50 mg/kg body weight to establish the rat model of mammary carcinogenesis, the ultrastructure changes of mammary gland cells in rats were observed by transmission electron microscope, the cell proliferation activity was detected by BrdU-labeled immunocytochemistry, and the expression of PPARbeta and PPARgamma mRNA were assayed by RT-PCR.
RESULTSThere was no breast cancer occurring in control groups and the MNU-treated n-3 PUFA group, and the ultrastructure and proliferation activity of mammary gland cells in these groups were normal. In contrast, there appeared obvious marker of adenocarcinomas in mammary gland cells of MNU-induced breast cancer, and a high cell proliferation activity was found in tumor growth-enhancing groups (SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and S/M/P, 21% - 22% of BrdU-labeled cells), while a low cell proliferation activity was detected in rats fed with 1:1 n-6/n-3 diet (13% of BrdU-labeled cells, P < 0.05). Moreover, peroxisome proliferator-activated receptors (PPARs), as important nuclear receptor genes of relating lipid metabolism, the expressions of PPARbeta and PPARgamma mRNA were significantly up-regulated in mammary adipose tissues of MNU-induced breast cancer as compared with the control groups, but the expression levels of peroxisome proliferator-activated receptors (PPARs) in rats fed with 1:1 n-6/n-3 group were lowest (P < 0.05).
CONCLUSIONThe different dietary fatty acid compositions should diversely adjust the expression of PPARs gene in rats, which maybe have an important role in affecting incidence of breast cancer.
Animals ; Fatty Acids ; pharmacology ; Fatty Acids, Omega-3 ; pharmacology ; Fatty Acids, Omega-6 ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Mammary Neoplasms, Experimental ; genetics ; PPAR gamma ; genetics ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley
2.Progress on relationship between omega-3 polyunsaturated fatty acids and violent-aggressive behavior.
Journal of Forensic Medicine 2010;26(6):454-459
The relationship between omega-3 polyunsaturated fatty acids (PUFAs) and violent-aggressive behavior has been payed attention since 1980s. Their correlation was explored by many epidemiological investigations, and the effect of PUFAs on prevention or reduction of violent-aggressive behavior in different groups were also affirmed by some intervention studies. This article summarized the previous studies and reviewed the history of epidemiological or intervention studies on PUFAs and its relationship with violent-aggressive behavior. It also presented the possible influencing factors in these studies and possible mechanisms.
Aggression
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Animals
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Dietary Fats, Unsaturated/pharmacology*
;
Dietary Supplements
;
Docosahexaenoic Acids/pharmacology*
;
Eicosapentaenoic Acid/pharmacology*
;
Fatty Acids, Omega-3/pharmacology*
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Fatty Acids, Omega-6/pharmacology*
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Fishes
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Folic Acid/metabolism*
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Humans
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Hydroxyindoleacetic Acid/metabolism*
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Norepinephrine/metabolism*
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Risk Factors
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Serotonin/metabolism*
;
Violence/prevention & control*
3.Effect of polyunsaturated fatty acids ω-3 and ω-6 on angiogenesis formation in human gastric cancer.
Jiachi MA ; Yuntao MA ; Tiankang GUO ; Quan CHEN ; Yiping LI ; He SU ; Xiaochang CHEN ; Xiaodan ZHAO ; Qinjin GUO ; Jianbo QI
Chinese Journal of Gastrointestinal Surgery 2017;20(1):84-89
OBJECTIVETo investigate the effects of polyunsaturated fatty acids (PUFA) ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.
METHODSThe effects of ω-3, ω-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of ω-3, ω-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without ω-3, ω-6, PGE2 and PGE3 were designed as the control.
RESULTSWith the increased concentration of ω-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2±3.0 to 32.8±2.1, which was higher than control group (21.2±3.2) respectively (both P<0.05). With the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8±2.0 to 11.0±2.1, which was lower than control group (22.1±3.0) respectively (both P<0.05). In the angiogenesis assay, compared with control group (standard number: 43 721±4 654), the angiogenesis ability of HUVECs was significantly enhanced by ω-6 in concentration-dependent manner (1 μmol/L group: 63 238±4 795, 10 μmol/L group: 78 166±6 123, all P<0.01). Meanwhile, with the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129±3 102 to 20 012±1 541(all P<0.01). The proliferation and migration ability of HUVECs were significantly promoted by ω-6 metabolites PGE2 (P<0.05) in a concentration-dependent manner. In contrast, ω-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner (all P<0.05). After rofecoxib (a COX-2 specific inhibitor) inhibited the expression of COX-2, the expression level of PGE2 was significantly decreased in a dose-dependent manner. In co-culture system, whose gastric cancer cells expressed positive COX-2, ω-6 could increase angiogenesis of gastric cancer cells(P<0.01), but ω-3 could inhibit such angiogenesis(P<0.01). In co-culture system, whose gastric cancer cells did not express COX-2, ω-3 could inhibit the angiogenesis of gastric cancer cells (P<0.05), but ω-6 had no effect on angiogenesis.
CONCLUSIONSThe PUFA ω-6 can enhance the angiogenesis via the promotion of proliferation and migration of HUVECs, and COX-2 and PGE2 may play an important role in this process, whereas, the ω-3 can inhibit the angiogenesis through its middle metabolites PGE3 to inhibit the proliferation and migration of HUVECs. Results of this experiment may provide a new approach to inhibit and prevent the spread of gastric cancer.
Alprostadil ; analogs & derivatives ; pharmacology ; Angiogenesis Inducing Agents ; metabolism ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Cell Count ; methods ; Cell Line, Tumor ; drug effects ; physiology ; Cell Migration Assays ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Coculture Techniques ; Cyclooxygenase 2 ; pharmacology ; Dinoprostone ; metabolism ; pharmacology ; Fatty Acids, Omega-3 ; pharmacology ; Fatty Acids, Omega-6 ; metabolism ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; physiology ; Humans ; Lactones ; pharmacology ; Neovascularization, Pathologic ; physiopathology ; Stomach Neoplasms ; physiopathology ; Sulfones ; pharmacology
4.Role of unsaturated fatty acids in the enhancement of muscarinic current by hyposmotic membrane stretch in guinea pig smooth muscle cells.
Yi-Feng CUI ; Lin LI ; Yong-Chun YU ; Zheng-Yuan JIN ; Zai-Liu LI ; Wen-Xie XU
Acta Physiologica Sinica 2003;55(1):96-100
To investigate the function of exogenous unsaturated fatty acids in hyposmotic membrane stretch enhancement of muscarinic current (ICCh) in antral circular smooth muscle cells of guinea pig, we recorded the membrane current with the conventional whole cell patch-clamp technique. I(CCh) elicited by 50 micromol/L carbachol (CCh) at the holding potential of 20 mV under isosmotic condition was taken as control. Hyposmotic membrane stretch increased I(CCh) to 226.0+/-21.0%. When the cells were pretreated with 5 micromol/L arachidonic acid (AA), linoleic acid (LA) or oleic acid (OA), I(CCh)was inhibited to 3.8+/-0.6%, 35.2+/-0.8% and 66.6+/-0.6% respectively. Hyposmotic membrane stretch increased I(CCh) to 106.0+/-2.5%, 173.2+/-6.8% and 222.1+/-11.0% of the control respectively. Five micromol/L AA inhibited hyposmotic membrane stretch-enhanced I(CCh) by 51.2+/-3.8%, while the control I(CCh) under isosmotic condition was inhibited by 96.2+/-1.6%. The results suggest that unsaturated fatty acids inhibited I(CCh) and the inhibitory effect is more significant when the unsaturation degree is increased. However, the unsaturated fatty acids are not involved in the increase of I(CCh) induced by hyposmotic membrane stretch.
Animals
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Fatty Acids, Unsaturated
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pharmacology
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Guinea Pigs
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Membrane Potentials
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drug effects
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Myocytes, Smooth Muscle
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cytology
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physiology
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Osmotic Pressure
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Patch-Clamp Techniques
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Pyloric Antrum
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cytology
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physiology
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Receptors, Muscarinic
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physiology
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Sodium Chloride
5.Identification of heplipin inducing apoptosis-related genes in KG-1 human leukemia cells by differential display RT-PCR.
Li LI ; Zhen-lan SONG ; Dong-gang XU ; Jia-xi WANG
Chinese Journal of Hematology 2007;28(1):22-26
OBJECTIVETo investigate whether Heplipin can induce KG-1 cell apoptosis and explore apoptosis related differentially expressed genes in KG-1 leukemia cell before and after Heplipin induction.
METHODSDNA distribution and DNA electrophoresis were used to prove that Heplipin can induce KG-1 cell apoptosis. The differential display reverse transcription-polymerase chain reaction (DDRT-PCR) was adopted to screen differentially expressed genes before and after Heplipin induction of KG-1 cells for 16 hours and 20 hours. The differentially expressed genes were cloned and analyzed.
RESULTSHeplipin could induce KG-1 cell apoptosis. There were differentially expressed genes in KG-1 cells before and after induction. Wnt13 and ATPase 3 were apoptosis related differentially downregulated genes after Heplipin induction. Conclusion Heplipin can induce KG-1 cell apoptosis. Heplipin induced KG-1 cell apoptosis is related with Wntl3 and ATPase3 (PSMC3). It is the first report that Wnt13 was detected in leukemia cell line.
ATPases Associated with Diverse Cellular Activities ; Apoptosis ; drug effects ; genetics ; Cell Line, Tumor ; Fatty Acids, Unsaturated ; pharmacology ; Gene Expression Profiling ; Humans ; Leukemia ; genetics ; pathology ; Proteasome Endopeptidase Complex ; genetics ; RNA, Messenger ; genetics ; Wnt Proteins ; genetics
6.Advances in the study of the chemical constituents and biological activities of 3 species of Echinacea.
Ji-ren LI ; Yu-ying ZHAO ; Tie-min AI
China Journal of Chinese Materia Medica 2002;27(5):334-337
Adjuvants, Immunologic
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pharmacology
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Animals
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Anti-Inflammatory Agents, Non-Steroidal
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pharmacology
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Antiviral Agents
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pharmacology
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Caffeic Acids
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chemistry
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isolation & purification
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pharmacology
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Drugs, Chinese Herbal
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isolation & purification
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pharmacology
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Echinacea
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chemistry
;
classification
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Fatty Acids, Unsaturated
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isolation & purification
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pharmacology
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Molecular Structure
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Plants, Medicinal
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chemistry
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Polyunsaturated Alkamides
7.Mechanism related to docosahexaenoic acid induced large conductance calcium-activated potassium channel currents increase in coronary smooth muscle cells.
Ru-xing WANG ; Ku-lin LI ; Chang-ying ZHANG ; Jie ZHENG ; Su-xia GUO ; Ying WU ; Xiao-rong LI ; Qiang CHAI ; Tong LU ; Hon-chi LEE
Chinese Journal of Cardiology 2011;39(4):348-352
OBJECTIVETo investigate the mechanism of enhanced large conductance calcium-activated potassium channel currents (BK) in coronary smooth muscle cells (SMCs) by docosahexaenoic acid (DHA).
METHODSCoronary SMCs were isolated by enzyme digestion. Potassium channels in coronary SMCs were identified by applications of different potassium blockers. Effects of DHA and its metabolite 16, 17-epoxydocosapentaenoic acid (16, 17-EDP) on BK channels in the absence and presence of cytochrome P450 epoxygenase inhibitor SKF525A were studied by patch clamp in whole-cell configuration.
RESULTSBK channels were widely distributed in SMCs, and BK currents in normal SMCs accounted for (64.2 ± 2.7)% of total potassium currents (n = 20). DHA could activate BK channels, and its 50% effective concentration (EC(50)) was (0.23 ± 0.03) µmol/L, however, the effect of DHA on BK channels was abolished after SMCs were incubated with cytochrome P450 epoxygenase inhibitor SKF525A. 16, 17-EDP, a metabolite of DHA, could reproduce the effects of DHA on BK channels, and its EC(50) was (19.7 ± 2.8) nmol/L.
CONCLUSIONDHA and metabolites can activate BK channels and dilate coronary arteries through activating cytochrome P450 epoxygenase pathway.
Animals ; Coronary Vessels ; cytology ; drug effects ; metabolism ; Cytochrome P-450 Enzyme Inhibitors ; Docosahexaenoic Acids ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Large-Conductance Calcium-Activated Potassium Channels ; metabolism ; Muscle, Smooth, Vascular ; drug effects ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Proadifen ; pharmacology ; Rats ; Rats, Sprague-Dawley
8.Effect of different parts of Portulace oleracea on the levels of TNF-alpha and IL-6 in the supernatant of cultured adipose cell.
Feng-ying XIAO ; Fu-er LU ; Li-jun XU
China Journal of Chinese Materia Medica 2005;30(22):1763-1766
OBJECTIVETo explore the effects of drug-carried serum of the different parts of Portulace olerace on cytokine TNF-alpha and IL-6 secreted by adipose cell in vitro.
METHODModels of adipose cell were established by Rodbell method. Using the method of seropharmacology, the drug-carried serum of the different parts of P. olerace were prepared. The cell viability of each group was tested by. Methy thiazolyl tetrazolium (MTT) assay. The levels of TNF-alpha and IL-6 in the supernatant of cultured adipose cell were assayed by RIA.
RESULTMTT assay results showed the cell viability of normal serum group was significantly higher than that of high lipid serum( P < 0.05). Compared with the high lipid serum group, the cell viability of the drug-carried serum groups in 40% and 20% concentration were significantly increased( P < 0.05). The high lipid serum had a better effect on increasing the levels of TNF-alpha and IL-6 than the normal serum group (P < 0.01). Expect the drug-carried serum of P. olerace low dose group in 20% concentration, each drug-carried serum group could markedly lower the levels of TNF-alpha (P < 0.05 or P < 0.01). Each drug-carried serum group in 40% concentration and the drug-carried serum P. olerace MS high dose group in 20% concentration could markedly lower the levels of IL-6 (P < 0.05 or P < 0.01).
CONCLUSIONThe drug-carried serum of P. olerace and its different parts act on adipose cell damaged by the high lipid serum, significantly increas the cell viability in the groups in 40% and 20% concentration, and improve the disorder of lipid in differeut degrel by lowering the levels of TNF-alpha and IL-6 that adipose cell secreted in vitro.
Adipocytes ; cytology ; metabolism ; Animals ; Cell Survival ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Fatty Acids, Unsaturated ; administration & dosage ; isolation & purification ; pharmacology ; Flavones ; administration & dosage ; isolation & purification ; pharmacology ; Hyperlipidemias ; blood ; Interleukin-6 ; metabolism ; Plants, Medicinal ; chemistry ; Portulaca ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Serum ; physiology ; Tumor Necrosis Factor-alpha ; metabolism
9.HIV-1 Rev and related inhibitors.
Acta Pharmaceutica Sinica 2007;42(4):347-351
HIV-1 Rev is an indispensable regulatory factor of the virion protein expression. The interaction between Rev and RRE RNA accelerates the nuclear export of viral mRNA. The unspliced and singly spliced mRNA will be degraded in the absence of Rev, resulting in the interception of HIV-1 replication at the same time. The pivotal role that Rev plays in HIV-1 replication as a trans-acting factor makes it a new target in the research of AIDS drugs. In this review, the function of Rev, Rev-RRE interaction, as well as their related inhibitors are reported.
Active Transport, Cell Nucleus
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Amino Acid Sequence
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Anti-HIV Agents
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chemistry
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pharmacology
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Cell Nucleus
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metabolism
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Fatty Acids, Unsaturated
;
chemistry
;
pharmacology
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Framycetin
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chemistry
;
pharmacology
;
HIV-1
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genetics
;
metabolism
;
physiology
;
Karyopherins
;
metabolism
;
RNA, Messenger
;
genetics
;
RNA, Viral
;
genetics
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Receptors, Cytoplasmic and Nuclear
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metabolism
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Transcription, Genetic
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Virus Replication
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rev Gene Products, Human Immunodeficiency Virus
;
antagonists & inhibitors
;
metabolism
10.12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid suppresses UV-induced IL-6 synthesis in keratinocytes, exerting an anti-inflammatory activity.
Jin Wook LEE ; Ho Cheol RYU ; Yee Ching NG ; Cheolmin KIM ; Jun Dong WEI ; Vikineswary SABARATNAM ; Jae Hong KIM
Experimental & Molecular Medicine 2012;44(6):378-386
12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is an enzymatic product of prostaglandin H2 (PGH2) derived from cyclooxygenase (COX)-mediated arachidonic acid metabolism. Despite the high level of 12-HHT present in tissues and bodily fluids, its precise function remains largely unknown. In this study, we found that 12-HHT treatment in HaCaT cells remarkably down-regulated the ultraviolet B (UVB) irradiation-induced synthesis of interleukin-6 (IL-6), a pro-inflammatory cytokine associated with cutaneous inflammation. In an approach to identify the down-stream signaling mechanism by which 12-HHT down-regulates UVB-induced IL-6 synthesis in keratinocytes, we observed that 12-HHT inhibits the UVB-stimulated activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kappaB). In addition, we found that 12-HHT markedly up-regulates MAPK phosphatase-1 (MKP-1), a critical negative regulator of p38 MAPK. When MKP-1 was suppressed by siRNA knock-down, the 12-HHT-mediated inhibitory effects on the UVB-stimulated activation of p38 MAPK and NF-kappaB, as well as the production of IL-6, were attenuated in HaCaT cells. Taken together, our results suggest that 12-HHT exerts anti-inflammatory effect via up-regulation of MKP-1, which negatively regulates p38 MAPK and NF-kappaB, thus attenuating IL-6 production in UVB-irradiated HaCaT cells. Considering the critical role of IL-6 in cutaneous inflammation, our findings provide the basis for the application of 12-HHT as a potential anti-inflammatory therapeutic agent in UV-induced skin diseases.
Anti-Inflammatory Agents, Non-Steroidal/pharmacology
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Cell Line
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Dual Specificity Phosphatase 1/biosynthesis/genetics
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Enzyme Activation
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Fatty Acids, Unsaturated/*pharmacology
;
Humans
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Interleukin-6/*biosynthesis
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Keratinocytes/*metabolism/radiation effects
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NF-kappa B/metabolism
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RNA Interference
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RNA, Small Interfering
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Receptors, Leukotriene B4/genetics
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Signal Transduction/drug effects
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Skin Diseases/drug therapy
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*Ultraviolet Rays
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Up-Regulation
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p38 Mitogen-Activated Protein Kinases/metabolism