ABSTRACT
Glaucomatous optic neuropathy(GON)is the difficulty of glaucoma treatment. In recent years, a variety of theories have been put forward about the pathogenesis of GON, but none of them can explain the principle of optic neuropathy caused by all types of glaucoma, which makes the disease difficult to treat in clinical treatment and is not conducive to early intervention. The latest research found that the transient receptor potential channel vanillic acid subfamily 4(TRPV4)in the retina plays an important role in various pathogenesis of GON. This article will review TRPV4 and its role in the occurrence and development of GON in order to find a common “connection point” for the multiple mechanism theories of GON, which will contribute to further understanding and clinical treatment of the disease.
ABSTRACT
Bladder cancer is a kind of urothelial cancer with high incidence and heterogeneity. From superficial bladder tumors to muscular invasive malignant tumors, due to their high-frequency recurrence and metastatic characteristics, they are inherently refractory. Although a comprehensive treatment with surgery as the main focus while chemotherapy, radiotherapy, and immunotherapy as a supplement has been formed, the limitations of chemotherapy regimens, the unpopularity of radiotherapy, and the low efficiency of immunotherapy, make clinical decision-making still difficult. Recently, a number of targeted therapies have emerged in bladder cancer and have shown good responses. Transient receptor potential (TRP) channel are novel therapeutic targets and current research hotspots in bladder cancer. This review discusses the anti-tumoral molecular mechanism of TRP channel in bladder cancer, its feasibility as a potential therapeutic target, and the prospects of drug combination to sensitize platinum-based chemotherapy.
ABSTRACT
Vascular smooth muscle cells (VSMCs) play a pivotal role in the stability and tonic regulation of vascular homeostasis. VSMCs can switch back and forth between highly proliferative (synthetic) and fully differentiated (contractile) phenotypes in response to changes in the vessel environment. Abnormal phenotypic switching of VSMCs is a distinctive characteristic of vascular disorders, including atherosclerosis, pulmonary hypertension, stroke, and peripheral artery disease; however, how the control of VSMC phenotypic switching is dysregulated under pathological conditions remains obscure. Canonical transient receptor potential (TRPC) channels have attracted attention as a key regulator of pathological phenotype switching in VSMCs. Several TRPC subfamily member proteins—especially TRPC1 and TRPC6—are upregulated in pathological VSMCs, and pharmacological inhibition of TRPC channel activity has been reported to improve hypertensive vascular remodeling in rodents. This review summarizes the current understanding of the role of TRPC channels in cardiovascular plasticity, including our recent finding that TRPC6 participates in aberrant VSMC phenotype switching under ischemic conditions, and discusses the therapeutic potential of TRPC channels.
Subject(s)
Atherosclerosis , Cell Plasticity , Homeostasis , Hypertension, Pulmonary , Muscle, Smooth, Vascular , Peripheral Arterial Disease , Phenotype , Plastics , Rodentia , Stroke , Transient Receptor Potential Channels , Vascular RemodelingABSTRACT
In acute hypoxia, pulmonary vascular will contract and divert blood to better ventilated area to optimize ventilation/perfusion matching, which is known as hypoxic pulmonary vasoconstriction (HPV). In chronic hypoxia, irreversible pulmonary vascular remodeling can be induced, characterized by pulmonary artery middle smooth muscle cells and the outer fiber cell hyperplasia in luminal stenosis and pulmonary artery hypertension (PAH) eventually. Furthermore, PAH can cause increased ventricular afterload, and right heart failure in severe cases. Pulmonary artery smooth muscle cell (PASMC) elevated Ca2+ concentration is one of the most important factors of its contractions, proliferation and migration. Recent studies on Ca2+ promoting in HPV were summarized in order to provide evidence for clinical prevention of hypoxia and therapeutic PAH.
ABSTRACT
Objective To investigate the expression and relationship of canonical transient receptor potential channel-3 (TRPC3) and brain-derived neurotrophic factor (BDNF) in the hippocampus of a rat model of Alzheimer's disease (AD). Methods SD rats were randomly divided into PBS, AD, and AD+BDNF experimental groups. AD models were generated by intracerebroventricular injection ofβ-amyloid protein (Aβ1-42). BDNF was injected via the lateral ventricle catheter after 14 days. The Morris water maze test was used to assess the spatial learning and memory ability of the rats. The expression of TRPC3 and BDNF mRNA and protein in the hippocampus were detected by RT-PCR and Western blotting, respectively. Results The Morris water maze test showed that the escape latencies of the fifth day in the AD group were longer than those in the PBS group (P ＜ 0. 05). The escape latencies in the AD+BDNF group were shorter than those in the AD group (P ＜ 0. 05). RT-PCR and Western blotting results showed that the expression of both TRPC3 and BDNF were reduced in the AD group compared with the PBS group (P ＜ 0. 05). TRPC3 expression was increased in the AD+BDNF group compared with the AD group (P ＜ 0. 05). Conclusion The expression of BDNF and TRPC3 is decreased in the hippocampus of AD rats. An exogenous BDNF injection appears to improve the spatial learning and memory of AD rats that are impaired by a Aβ1-42 injection, possibly via TRPC3 upregulation, and may play a protective role in neurons.
ABSTRACT
Objective@#To understand the changes of serum transient receptor potential channel 1(TRPC1) in patients with vascular depression.@*Methods@#58 patients with vascular depression, 49 patients with major depressive disorder and 38 healthy controls were recruited.The TRPC1 of all subjects were detected by ELISA.Patients with vascular depression and patients with primary depression were scaled by HAMD-17.The level of TRPC1 was contrasted in different ages groups and in different nosogenesis (cerebral infarction, ischemic cerebrovascular disease, old cerebral hemorrhage, cerebral microbleeds, vascular risk factors, etc.) of vascular depression.The relationship between TRPC1 level and severity of depressive symptoms was further analyzed.@*Results@#(1)The level of TRPC1 of serum((643.76±118.43)pg/ml) was decreased in patients with vascular depression compared with that in healthy controls ((712.48± 98.75) pg/ml). The level of TRPC1 in patients with vascular depression over 60 years ((601.43±113.55)pg/ml)was lower than that in patients with major depressive disorder over 60 years ((626.32±125.46)pg/ml) and healthy controls over 60 years((721.84± 99.62)pg/ml) .(2) Among the various causes of vascular depression, the level of TRPC1 in patients with cerebral infarction, ischemic cerebrovascular disease and cerebral microbleeds was significantly lower (P<0.05). (3) The levels of TRPC1 in the patients with vascular depression (r=-0.962, P<0.05) and patients with major depressive disorder (r=-0.674, P<0.05) were negatively correlated with HAMD-17 score.@*Conclusion@#The level of TRPC1 is lower in patients with vascular depression, which is more obvious in patients with cerebral infarction, ischemic cerebrovascular disease, and cerebral microhaemorrhage.The lower the level of TRPC1, the more severe the depression.The neuroprotective effect of TRPC1 is reduced in patients with vascular depression.The TRPC1 can be used as a biomarker for vascular depression.
ABSTRACT
Transient receptor potential (TRP) channels are non-selective and cation-permeable channels in the cell membrane, widely distributed in tissues and organs of human body. As biosensors, TRP channels can regulate the functions of vision, hearing, taste, pain, and touch, etc. So far, more than 100 different kinds of natural modulators targeting TRP channels have been identified from 70 species of plants or animals. In this review article, we attempt to summarize the effect of known natural active compounds on TRP channels with focuses on their sources, structures, action features and mechanisms. Hopefully this review can provide some useful information that can facilitate discovery of more specific natural modulators, and development of innovative therapeutic drugs targeting TRP channels.
ABSTRACT
Objective To investigate the effect of thymopentin combined with routine medication on serum interleukin 17A(IL-17A),chemokine 12 (CXCL12) levels and transient receptor potential channel 1 (TRPC1)expression in elderly patients with chronic obstructive pulmonary disease (COPD).Methods 156 COPD patients were selected as study objects.They were randomly divided into two groups(n =78) according to the digital table.The control group received routine treatment,and the observation group received subcutaneous injection of thymopentin on the basis of routine treatment.Before and after treatment,the CD3+,CD4+,CD8+,CD4+/CD8+ levels were tested to compare the immunologic function of the two groups.Before and after treatment,the FEV1,FEV1/FVC,PEF were tested to compare the pulmonary ventilation function of the two groups.The IL-17A,CXCL12 levels in peripheral blood and TRPC1 level in bronchoalveolar liquid before and after treatment were tested and compared between the two groups.The adverse effect was compared.Results Before treatment,the CD3+,CD4+,CD8+ and CD4+/CD8+ between the two groups had not statistically significant differences (all P ＞ 0.05),which of the control group after treatment had no significant change (all P ＞ 0.05),the CD3+,CD4+,CD4+/CD8+ of the observation group [(65.17 ± 2.39) ％,(41.06 ±2.15) ％,(1.50 ± 0.74) ％] were significantly higher than control group [(52.66 ± 2.38) ％,(32.30 ± 2.05) ％,(0.80 ± 0.81) ％] (all P ＜ 0.05),and the CDs+ of the observation group [(24.02 ± 2.23) ％] was significantly lower than control group[(32.66 ± 1.97) ％,P ＜0.05].Before treatment,the FEV1,FEV1/FVC,PEF,the IL-17A,CXCL12 levels and TRPC1 level had no statistically significant differences between the two groups(P ＞ 0.05).After treatment,the peripheral blood IL-17A [(24.18 ± 3.69) pg/mL],CXCL12 levels [(193.50 ± 2.90) pg/mL] and TRPC1 level in BALF [(7.69 ± 1.14)ng/L] in the observation group decreased significantly(P ＜ 0.05),which in the control group also decreased significantly [IL-17A (34.25 ± 3.74) pg/mL,CXCL12 (205.37 ± 3.21) pg/mL,TRPC1 (14.25 ± 1.20)ng/L] (P ＜ 0.05),which of the observation group were significantly lower than those of the control group(all P ＜0.05).The incidence rates of adverse effects of the two groups were t6.67％,12.82％,there was no statistically significant difference(P ＞ 0.05).Conclusion Thymopentin combined with conventional therapy can effectively improve the elderly COPD patients'immunologic function and pulmonary ventilation function,decrease the inflammatory factor,relieve inflammatory reaction and it is safe and effective.
ABSTRACT
Objective To investigate the effect of transient receptor potential M4 (TRPM4) on autonomous regulation disorder of cerebral blood flow following subarachnoid hemorrhage (SAH) in rats.Methods A total of 120 clean grade male SD rats were selected.They were divided into sham operation,SAH,negative control,and treatment groups according to the random number table.The dead rats were excluded.A SAH model was induced by using the suprasellar cistern injection method with a stereotaxic apparatus.Isotonic saline 0.2 ml was injected into the rats of the sham operation group and negative control group respectively,and autologous tail arterial blood 0.2 ml was injected into the rats of the SAH group and the treatment group respectively.The isotonic saline solution was continuously pumped into lateral ventricle of rats via implantable micro-pump in the sham operation group and the SAH group respectively,and the concentration of 0.03 mol/L of TRPM4 blocking agent was continuously pumped into the lateral ventricles of rats in the control group and the treatment group respectively.The 4 groups of rats received the regional cerebral blood flow and whole cerebral blood flow detection on day 3,5,and 7,respectively.Results One hundred and six (88.3%) of the 120 SD rats survived to the time point of study,data analyses were performed in the 4 groups (with 21 rats in each group) respectively (n=7 in each time point).There were significant differences in cerebral cortex local and whole cerebral blood flow at day 3,5,and 7 in the sham operation,SAH and negative control groups (all P<0.05).Cerebral cortex local cerebral blood flow (141±18,148±24,and 168±19 PU,respectively at day 3,5,and 7) and whole cerebral blood flow (93±5,85±5,and 85±6 ml/[100 g·min],respectively at day 3,5,and 7 in the SAH group) were decreased significantly compared with the sham operation group (cortex local cerebral blood flow:235±17,220±24,and 224±20 PU),whole cerebral blood flow (141±10,147±8,and 143±8 ml/[100 g·min]),all P<0.05).Cerebral cortex local and whole cerebral blood flow (cortical local cerebral blood flow:183±26,173±26,and 187±15 PU,whole brain:114±10,104±9,and 119±5 ml/(100 g·min) in the treatment group were significantly increased compared with the SAH group (all P<0.05).Conclusion TRPM4 has an obvious effect on improving the autonomous regulation disorder of cerebral blood flow after SAH.
ABSTRACT
AIM: To investigate the effects of transient receptor potential channel 6 (TRPC6) on the proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) induced by IL-1β.METHODS: The mRNA expression of TRPC6 in synovial tissues from RA or OA patients was studied by RT-qPCR.RA-FLS were cultured by enzyme digestion and tissue adhesion methods.The method of flow cytometry was applied to identify the RA-FLS.RA-FLS were treated with different concentrations (0, 0.25, 0.5, 1, 2, 4, 8 and 16 μg/L) of IL-1β for 36 h.The cell viability was examined by CCK-8 assay.RA-FLS were incubated with IL-1β (16 μg/L) for different time (12, 24, 36, 48, 60 and 72 h), and the cell viability was measured by CCK-8 assay.The interference efficiency of TRPC6-siRNA was determined by RT-qPCR and Western blotting.After incubation in the presence or absence of IL-1β medium, the cell viability, the percentage of EdU-positive cells and the percentage of (G2/M+S) phase were measured by CCK-8 assay, EdU labeling assay and flow cytometry, respectively.RESULTS: The mRNA expression of TRPC6 was found in synovial tissue with higher levels in RA patients than that in OA patients.TRPC6-siRNA significantly decreased the mRNA and protein expression of TRPC6 (P<0.05).When RA-FLS were treated with IL-1β, the proliferation of RA-FLS was increased (P<0.05).The differences of the cell viability, the percentage of EdU-positive cells and the (G2/M+S) phase percentage between TRPC6-siRNA group and blank control group or NC-siRNA group were significant, in the presence of IL-1β (P<0.05).However, they were not significant in the absence of IL-1β.CONCLUSION: TRPC6 is involved in the proliferation of RA-FLS induced by IL-1β.Silencing of TRPC6 gene inhibits the growth of RA-FLS induced by IL-1β.
ABSTRACT
Pain, as one of the most common clinical symptoms, seriously affects the quality of life of patients.Transient Re-ceptor Potential Vanilloid Type 1 (TRPV1) and Purinergic receptor(P2X3)are both involved in the transmission of a variety of patho-logical pain signals.Their interaction is less reported.This article reviews the interaction between TRPV1 and P2X3 in the pain signal transduction, and provides a new way for the treatment of pain.
ABSTRACT
Objective To investigate the membrane topology of transient receptor potential(TRP)channel. Methods Glycosylation method was used to investigate the membrane integrations of each hydrophobic segment of canonical TRP(TRPC5). Results In TRPC5 channel,S4?S8 segments were integrated into membrane with Ncyt/Cexo and Nexo/Ccyt orientations sequentially ,and C?terminus was intracellular. S1?S3 segments were integrated into membrane with two possible types. One was that S1 and S3 were integrated into membrane,whereas S2 was left out of the membrane on the cytosolic side;and the other was a mixed type that S1 and S3 were exposed to cytoplasm respectively. Both of them,the N?termi?nus was intracellular. Conclusion S4?S8 segments of TRPC5 are transmembrane segments. The integrations of S1?S3 segments into membrane need to be further investigated.
ABSTRACT
Objective To investigate the protein expression of the canonical transient receptor potential(TRPC)channel in the hippocampus of amyloidβprotein(Aβ)?induced Alzheimer’s disease(AD)mice. Methods A total of 36 ICR mice were randomly divided into AD group and control group,with 18 rats in each group. AD mice models were established by Aβ1?42 microinjection into the lateral intracerebroventricular. Learning and memory abilities of the mice were determined using Morris water maze. All TRPC1?TRPC7 mRNA levels in the hippocampus of the mice were detected using reverse transcriptase polymerase chain reaction(RT?PCR). Hippocampal TRPC4 protein expression was examined using immunofluorescence and Western blotting methods. Results Water maze test results showed that the escape latency of AD group were significant?ly longer than that of the control group(P<0.01),and that the target quadrant occupancy of AD group was significantly shortened(P<0.01)and the frequency of platform crossing of AD group was significantly reduced(P<0.01). RT?PCR results showed that all TRPC(TRPC1?TRPC7) mRNA were expressed in the hippocampal of both AD group and control group. Among these channels ,only TRPC4 mRNA levels of AD group was higher than that of the control group(P<0.01). Immunofluorescence images showed that TRPC4 expressed on the membrane of neurons and the intensities of the immunofluorescence of TRPC4 in AD group were stronger than that of control group. Western blotting results showed that the TRPC4 protein expression of AD group was higher than that of control group(P<0.05). Conclusion The increase of TRPC4 protein expression in the hippocampus of mice after intracerebroventricular injection of Aβ1?42 oligomers suggests that TRPC4 may be involved in the pathogenesis of AD induced by calcium homeostasis.
ABSTRACT
AIM:To study the effect of transient receptor potential channel 1 ( TRPC1) on the survival of hip-pocampal neurons in mice.METHODS:TRPC1 knockout mice and the control mice (6 months old) were used in this study.Immunofluorescence staining of neuron-specific marker NeuN, Nissl staining and TUNEL staining were performed to measure the changes of the neurons in hippocampal CA1, CA3 and dentate gyrus (DG).Western blot analysis was used to detect the levels of pro-apoptotic protein C/EBP homologous protein ( CHOP) and cleaved caspase-3.RESULTS:Immuno-fluorescence staining and Nissl staining showed that the number of neuronal cells was significantly decreased in hippocampal CA1, CA3 and DG of TRPC1 knockout mice compared with the control mice.TUNEL staining showed that the apoptosis neuronal cell number of the above areas in TRPC1 knockout mice was significantly increased compared with the control mice.The results of Western blot revealed that the levels of CHOP and cleaved caspase-3 were significantly increased in the hippocampus of TRPC1 knockout mice relative to the control mice.CONCLUSION:The depletion of TRPC1 induces neu-ronal loss through a mechanism of TRPC1-mediated apoptosis.
ABSTRACT
AIM:To investigate the effects of vesicular transport inhibition on the proliferation and regulation of store-operated calcium entry ( SOCE) in rat endothelial progenitor cells ( EPCs) .METHODS:EPCs were isolated from the rats with density-gradient centrifugation and confirmed via double fluorescence staining with acLDL-DiI and FITC-UEA-I.After inhibition of vesicular transport with brefeldin A ( BFA) , the proliferation of EPCs was measured by CCK-8 assay and real-time cell analyzer instrument, apoptosis was analyzed by flow cytometry, and the expression of ADP-ribosylation factor GTPase-activating protein 1 (ARFGAP1), a key protein to vesicular transport, was also detected.SOCE was ob-served under laser scanning confocal microscope after the vesicular transport was inhibited, and the protein expression of SOCC complex was determined by Western blot.Furthermore, the influences of vesicular transport inhibition on the expres-sion of transient receptor potential channel 1 ( TRPC1 ) and SOCE were examined with a RNA interference method.RE-SULTS:The acLDL-DiI and FITC-UEA-I double positive rate of the cells was 82.53%±6.12%.BFA insult significantly inhibited the proliferation of EPCs and down-regulated the expression of ARFGAP1, and no influence on the apoptosis of the EPCs was observed, suggesting that vesicular transport of EPCs was inhibited.Vesicular transport inhibition remarkably down-regulated the expression of TRPC1 and decreased SOCE level.No evident difference in the level of SOCE between siTRPC1 group and siTRPC1+BFA group, in which the cells were pretreated with siTRPC1 before BFA addition, was ob-served.CONCLUSION:Vesicular transport inhibition in EPCs reduces the proliferation of EPCs and decreases SOCE lev-el through down-regulation of TRPC1.
ABSTRACT
Brown adipose tissue (BAT) is a site of sympathetically activated non-shivering thermognenesis during cold exposure and after spontaneous hyperphagia, thereby involving in the autonomic regulation of energy balance and body fatness. Recent radionuclide studies have demonstrated the existence of metabolically active BAT in adult humans. Human BAT is activated by acute cold exposure, particularly in winter, and contributes to cold-induced increase in whole-body energy expenditure. The metabolic activity of BAT is lower in older and obese individuals. The inverse relationship between the BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. In fact, either repeated cold exposure or daily ingestion of some food ingredients acting on transient receptor potential channels recruited BAT in association with increased energy expenditure and decreased body fatness. Thus, BAT is a promising target for combating obesity and related metabolic disorders in humans.
Subject(s)
Adult , Animals , Humans , Mice , Adipose Tissue , Adipose Tissue, Brown , Eating , Energy Metabolism , Hyperphagia , Obesity , Transient Receptor Potential ChannelsABSTRACT
Objective To study the expression of transient receptor potential channel (TRPC) isoforms (TRPC1,3,4,5,6,7) inrats with cardiac hypertrophy.Methods Thirty adult male SD rats,weighing 200-240 g were divided into surgical group (model group,20 rats) and sham group (control group,10 rats) by random number table according to body weight.Aortic coarctation surgery was performed to establish a rat model of myocardial hypertrophy and the control group did not ligate thoracic aorta,but the same surgical procedure with the model group was performed.After 10 weeks,echocardiography was used to check changes of cardiac function; cardiac tissues of rats were weighed and cardiac hypertrophy index was calculated.Cardiac HE staining was used for observation of myocardial tissue morphological changes.Quantitative RT-PCR method was used for measuring the mRNA expression of TPRC isoforms (TRPC1,3,4,5,6,7).Western blotting assay was applied to detect the protein expression of TRPC4 and TPRC5 in hypertrophic cardiac tissue of rats.The relationship between cardiac hypertrophy exponential and TRPC4,TRPC5 protein expression was studied.Results Echocardiography showed that the septal thickness and posterior wall thickness in model group increased significantly compared with those of the control group [mm:(2.64 ± 0.31) vs.(1.89 ± 0.15),(2.30 ± 0.14) vs.(1.60 ± 0.09),t =9.19,8.57,all P ＜ 0.05].Compared with the control group,cardiac hypertrophy index was significantly increased in model group [(3.21 ± 0.15)vs.(1.82 ± 0.10)mg/g,t =17.02,P ＜ 0.01].HE staining of myocardium showed that cardiomyocyte hypertrophy,abnormal nuclear morphology and significantly enlarged nuclear,and hyperplasia of myocardial interstitial fibrous connective tissue could be seen in model group.The mRNA expression of TRPC4 and TRPC5 was significantly increased in the model group as compared to those of the control group (1.51 ± 0.48 vs.1.22 ± 0.25,1.65 ± 0.35 vs.1.27-± 0.87,t =3.55,4.65,all P ＜ 0.05).The protein expression of TRPC4 and TRPC5 was significantly increased in the model group as compared to those of the control group (1.00 ± 0.54 vs.1.45 ± 0.68,1.00 ± 0.65 vs.1.58 ±0.93,t =5.51,7.10,all P ＜ 0.05).The protein expression of TRPC4 and TPRC5 were associated with cardiac hypertrophy index (r =0.728,0.681,all P ＜ 0.05).Conclusion Expression of TRPC4 and TRPC5 is increased in rats with cardiac hypertrophy.
ABSTRACT
[ ABSTRACT] AIM:To investigate the role of canonical transient receptor potential channel 1 ( TRPC1 ) in the epithelial-mesenchymal transition ( EMT) of human bronchial epithelial ( HBE) cells induced by transforming growth fac-tor-β1 (TGF-β1).METHODS:EMT of 16HBE cells induced by TGF-β1 were identified by microscopy, immunofluores-cence and Western blotting.Immunofluorescence, real-time PCR and Western blotting were applied to detect the mRNA and the protein expression of TRPC1 in the 16HBE cells.The influence of SKF96365 (a TRPC1 blocker) and siRNA-me-diated silencing of TRPC1 on the EMT of the 16HBE cells were detected by microscopy and Western blotting.RESULTS:Treatment with TGF-β1 induced significant morphological changes of the 16HBE cells.Exposure to TGF-β1 decreased the expression of E-cadherin protein (P<0.01) and increased the expression of α-SMA protein (P<0.05) in the 16HBE cells.Immunofluorescence observation indicated that TRPC1 expression in the 16HBE cells was positive.The expression of TRPC1 at mRNA and protein levels was significantly increased in the 16HBE cells after stimulation with TGF-β1 ( P<0.05).The morphological changes of the 16HBE cells induced by TGF-β1 were inhibited by SKF96365 and TRPC1 silen-cing compared with TGF-β1 group.The protein expression of E-cadherin andα-SMA induced by TGF-β1 were inhibited by SKF96365 and TRPC1 silencing compared with TGF-β1 group (P<0.05).CONCLUSION:TGF-β1 induces EMT with the mechanism of up-regulating TRPC1 in human bronchial epithelial cells.
ABSTRACT
Objective To explore the expression of transient receptor potential channel 6(TRPC6)in human breast cancer cells, and to clarify the correlation of TRPC6 with the invasion potential of breast cancer cells. Methods The human breast cancer cell strains MCF-7 (hypo-invasion group)and MDA-MB-231 (hyper-invasion group)were cultured.The expressions of TRPC6 mRNA and protein in in two groups were detected by RT-PCR and Western blotting methods.Then the MDA-MB-231 cells were divided into control group and SKF96365 group, the effects of SKF96365 on the invasion ability of MDA-MB-231 cells invitro were explored by wound healing assay and Transwell experiment.Results The results of Western blotting and RT-PCR showed that the expression levels of TRPC6 mRNA and protein in MDA-MB-231 cells were higher than that in MCF-7 cells(P<0.05).The wound healing assay showed the numbers of migrating cells in 5,25 and 40μmol·L-1 SKF96365 groups (76.24±7.54, 45.33±4.50,25.12±1.57)were lower than those in control group (130.48±9.55)(P<0.05).The Transwell experiment results indicated that the invasiveness of MDA-MB-231 cells were inhibited significantly by SKF96365 compared with control group (P<0.05).Conclusion The invasion ability of human breast cancer MDA-MB-231 cells is promoted by upregulating the TRPC6 expression, which indicates that the TRPC6 may play role in the metastasis of human breast cancer.
ABSTRACT
Brown adipose tissue (BAT) is recognized as the major site of sympathetically activated nonshivering thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controling whole-body energy expenditure and body fat. In adult humans, BAT has long been believed to be absent or negligible, but recent studies using fluorodeoxyglucose-positron emission tomography, in combination with computed tomography, demonstrated the existence of metabolically active BAT in healthy adult humans. Human BAT is activated by acute cold exposure, being positively correlated to cold-induced increases in energy expenditure. The metabolic activity of BAT differs among individuals, being lower in older and obese individuals. Thus, BAT is recognized as a regulator of whole-body energy expenditure and body fat in humans as in small rodents, and a hopeful target combating obesity and related disorders. In fact, there are some food ingredients such as capsaicin and capsinoids, which have potential to activate and recruit BAT via activity on the specific receptor, transient receptor potential channels, thereby increasing energy expenditure and decreasing body fat modestly and consistently.