Insects are poikilothermic animals,and temperature is one of the most important abiotic factors affecting their spread and distribution.For example,differences in thermal tolerance may underlie the significant differe...Insects are poikilothermic animals,and temperature is one of the most important abiotic factors affecting their spread and distribution.For example,differences in thermal tolerance may underlie the significant differences in geographical distributions between the native AsiaII3 and invasive MED(Mediterranean)cryptic Bemisia tabaci species in China.Transient receptor potential(TRP)channels are key components of the insect temperature perception system and act as molecular thermometers since they can be activated by specific changes in temperature.In this study,we cloned and characterized the AsiaII3 BtTRP gene and revealed its functions in the response to thermal stress.The full-length cDNA of BtTRP was 3821 bp,with a 3501-bp open reading frame encoding a 132.05-kDa protein.Comparing the deduced amino acid sequences of AsiaII3 BtTRP and MED TRP revealed five amino acid differences.In situ hybridization indicated that BtTRP might be widely expressed throughout the AsiaII3 adult body.BtTRP mRNA expression reached the highest levels after exposure to mild thermal stimuli(12 and 35°C),showing that BtTRP expression can be induced by temperature stress.Furthermore,the thermal tolerance of AsiaII3 after BtTRP dsRNA feeding was significantly lower than that of the control.Taken together,the present study highlights the importance of TRP channels for B.tabaci thermal resistance,and allows us to infer that the differences in amino acids between AsiaII3 and MED might cause the differences in thermal tolerance of these two cryptic species.This study provides a new direction for investigating geographic distribution differences between invasive and native insects.展开更多
Background: Natural killer (NK) cell phenotypes have reported to be implicated in the pathomechanism of Multiple Sclerosis (MS). Several investigators have observed reduced peripheral numbers, reduced cytotoxic activi...Background: Natural killer (NK) cell phenotypes have reported to be implicated in the pathomechanism of Multiple Sclerosis (MS). Several investigators have observed reduced peripheral numbers, reduced cytotoxic activity, and altered CD56Dim and CD56Bright NK cell phenotypes. This current project, for the first time, investigates the NK cell cytotoxicity, calcium mobilisation and transient receptor potential melastatin 3 (TRPM3) surface expression. Methods: NK cell cytotoxic activity and calcium signaling were examined in CD56Dim and CD56Bright NK cells before and after stimulation using Ionomycin, Pregnenolone sulphate, 2-Aminoethoxydiphenyl borate and Thapsigargin. Purified NK cells were labelled with antibodies to determine TRPM3, CD69 and CD107a surface expression using flow cytometry. Results: Twenty-two MS patients and 22 healthy controls were recruited for this project. Twelve of the 22 previously received Alemtuzumab (Lemtrada®) and the remaining ten reported nil medication. We report TRPM3 was significantly increased in untreated MS patients compared with healthy controls and treated MS patients (p-value 0.034). There was a significant decrease in CD69 surface expression on CD56Dim NK cell phenotype for untreated MS patients (p-value 0.031) and treated MS patients (p-value 0.036). We report altered calcium mobilisation in CD56Bright NK cells and to a lesser extent CD56Dim NK cells between healthy controls, treated and untreated MS patients. Conclusion: This investigation suggests variations in TRPM3 expression and calcium mobilisation of NK cells may be implicated in the pathogenesis of MS. Further investigation is required to determine the mechanism by which alemtuzumab alters calcium signaling in NK cells.展开更多
The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating m...The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating mechanism is dependent on reactive oxygen species. In pathological conditions, transient receptor potential melastatin 2 is overactivated, leading to a Ca~(2+) influx that alters cell homeostasis and promotes cell death. The role of transient receptor potential melastatin 2 in neurodegenerative diseases, including Alzheimer's disease and ischemia, has already been described and reviewed. However, data on transient receptor potential melastatin 2 involvement in Parkinson's disease pathology has emerged only in recent years and the issue lacks review studies that focus specifically on this topic. The present review aims to elucidate the role of the transient receptor potential melastatin 2 channel in Parkinson's disease by reviewing, summarizing, and discussing the in vitro, in vivo, and human studies published until August 2022. Here we describe fourteen studies that evaluated the transient receptor potential melastatin 2 channel in Parkinson's disease. The Parkinson's disease model used, transient receptor potential melastatin 2 antagonist and genetic approaches, and the main outcomes reported were discussed. The studies described transient receptor potential melastatin 2 activation and enhanced expression in different Parkinson's disease models. They also evidenced protective and restorative effects when using transient receptor potential melastatin 2 antagonists, knockout, or silencing. This review provides a literature overview and suggests where there is a need for more research. As a perspective point, this review shows evidence that supports transient receptor potential melastatin 2 as a pharmacological target for Parkinson's disease in the future.展开更多
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling condition of unknown cause having multi-system manifestations. Our group has investigated the potential role of transient receptor potential (...Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling condition of unknown cause having multi-system manifestations. Our group has investigated the potential role of transient receptor potential (TRP) ion channels in the etiology and pathomechanism of this illness. Store-operated calcium entry (SOCE) signaling is the primary intracellular calcium signaling mechanism in non-excitable cells and is associated with TRP ion channels. While the sub-family (Canonical) TRPC has been traditionally associated with this important cellular mechanism, a member of the TRPM sub-family group (Melastatin), TRPM3, has also been recently identified as participating in SOCE in white matter of the central nervous system. We have identified single nucleotide polymorphisms (SNPs) in TRP genes in natural killer (NK) cells and peripheral blood mononuclear cells (PBMCs) in CFS/ME patients. We also describe biochemical pathway changes and calcium signaling perturbations in blood cells from patients. The ubiquitous distribution of TRP ion channels and specific locations of sub-family group members such as TRPM3 suggest a contribution to systemic pathology in CFS/ME.展开更多
目的探讨TRPC3基因多态性与原发性高血压患者左心室肥厚(LVH)的关系。方法305例原发性高血压患者根据左心室质量指数(LVMI)分为单纯高血压224例(对照组)和高血压合并LVH 81例(LVH组)。分析2组年龄、吸烟史等一般资料差异。留取外周血标...目的探讨TRPC3基因多态性与原发性高血压患者左心室肥厚(LVH)的关系。方法305例原发性高血压患者根据左心室质量指数(LVMI)分为单纯高血压224例(对照组)和高血压合并LVH 81例(LVH组)。分析2组年龄、吸烟史等一般资料差异。留取外周血标本,采用Sequenom MassARRAY®SNP检测技术对TRPC3基因单核苷酸多态性(SNP)位点Rs2292232、Rs4995894、Rs4292355进行基因分型。Logistic回归分析影响患者LVH的因素。结果(1)2组年龄、吸烟史、饮酒史、家族史、尿素、肌酐、空腹血糖、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、24 h平均舒张压(24 h DBP)差异无统计学意义(P>0.05),LVH组较对照组男性比例降低,而24 h平均收缩压(24 h SBP)、体质量指数(BMI)升高(P<0.05)。(2)2组Rs4995894及Rs4292355位点等位基因频率、基因型频率分布差异无统计学意义(P>0.05),TRPC3基因SNP位点Rs2292232基因型频率和等位基因频率分布差异有统计学意义(P<0.05),其中LVH组Rs2292232位点TT基因型频率较对照组更高(P<0.05)。(3)Logistic回归分析显示,女性(OR=0.332,95%CI:0.181~0.610)、较高24 h SBP(OR=1.035,95%CI:1.014~1.056)、TRPC3基因SNP Rs2292232 TT基因型(OR=2.105,95%CI:1.109~3.995)为原发性高血压患者发生LVH的独立危险因素(均P<0.05)。结论TRPC3基因Rs2292232位点SNP与高血压患者发生LVH有关,其中TT基因型患者更易发生LVH。展开更多
目的探讨经典瞬时受体电位通道蛋白3(TRPC3)与脑源性神经营养因子(BDNF)在阿尔茨海默病(AD)大鼠模型海马组织中的表达及其相互关系。方法将SD大鼠随机分为PBS组、AD组和AD+BDNF组。采用β-淀粉样蛋白(Aβ1-42)侧脑室注射,制备AD模型。B...目的探讨经典瞬时受体电位通道蛋白3(TRPC3)与脑源性神经营养因子(BDNF)在阿尔茨海默病(AD)大鼠模型海马组织中的表达及其相互关系。方法将SD大鼠随机分为PBS组、AD组和AD+BDNF组。采用β-淀粉样蛋白(Aβ1-42)侧脑室注射,制备AD模型。BDNF在造模14 d后经侧脑室导管注入。Morris水迷宫实验测定大鼠的空间学习记忆能力。实时PCR和Western blotting分别检测海马组织中TRPC3和BDNF m RNA和蛋白的表达情况。结果 Morris水迷宫实验表明,AD组大鼠第5天逃避潜伏期较PBS组延长(P<0.05);AD+BDNF组大鼠的逃避潜伏期较AD组缩短(P<0.05)。实时PCR及Western blotting结果表明,与PBS组相比,TRPC3和BDNF m RNA和蛋白在AD组表达均降低(P<0.05);与AD组相比,TRPC3 m RNA和蛋白在AD+BDNF组表达均增高(P<0.05)。结论 BDNF和TRPC3在AD大鼠海马组织表达降低;外源性BDNF可能通过上调TRPC3表达,从而改善Aβ1-42导致的AD大鼠空间学习记忆障碍,起到保护神经元的作用。展开更多
基金This work was funded by the National Natural Science Foundation of China(31672088 and 31601695)the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(caascx-2017-2022-IAS)the National Key Research and Development Program of China(2016YFC1200603).
文摘Insects are poikilothermic animals,and temperature is one of the most important abiotic factors affecting their spread and distribution.For example,differences in thermal tolerance may underlie the significant differences in geographical distributions between the native AsiaII3 and invasive MED(Mediterranean)cryptic Bemisia tabaci species in China.Transient receptor potential(TRP)channels are key components of the insect temperature perception system and act as molecular thermometers since they can be activated by specific changes in temperature.In this study,we cloned and characterized the AsiaII3 BtTRP gene and revealed its functions in the response to thermal stress.The full-length cDNA of BtTRP was 3821 bp,with a 3501-bp open reading frame encoding a 132.05-kDa protein.Comparing the deduced amino acid sequences of AsiaII3 BtTRP and MED TRP revealed five amino acid differences.In situ hybridization indicated that BtTRP might be widely expressed throughout the AsiaII3 adult body.BtTRP mRNA expression reached the highest levels after exposure to mild thermal stimuli(12 and 35°C),showing that BtTRP expression can be induced by temperature stress.Furthermore,the thermal tolerance of AsiaII3 after BtTRP dsRNA feeding was significantly lower than that of the control.Taken together,the present study highlights the importance of TRP channels for B.tabaci thermal resistance,and allows us to infer that the differences in amino acids between AsiaII3 and MED might cause the differences in thermal tolerance of these two cryptic species.This study provides a new direction for investigating geographic distribution differences between invasive and native insects.
文摘Background: Natural killer (NK) cell phenotypes have reported to be implicated in the pathomechanism of Multiple Sclerosis (MS). Several investigators have observed reduced peripheral numbers, reduced cytotoxic activity, and altered CD56Dim and CD56Bright NK cell phenotypes. This current project, for the first time, investigates the NK cell cytotoxicity, calcium mobilisation and transient receptor potential melastatin 3 (TRPM3) surface expression. Methods: NK cell cytotoxic activity and calcium signaling were examined in CD56Dim and CD56Bright NK cells before and after stimulation using Ionomycin, Pregnenolone sulphate, 2-Aminoethoxydiphenyl borate and Thapsigargin. Purified NK cells were labelled with antibodies to determine TRPM3, CD69 and CD107a surface expression using flow cytometry. Results: Twenty-two MS patients and 22 healthy controls were recruited for this project. Twelve of the 22 previously received Alemtuzumab (Lemtrada®) and the remaining ten reported nil medication. We report TRPM3 was significantly increased in untreated MS patients compared with healthy controls and treated MS patients (p-value 0.034). There was a significant decrease in CD69 surface expression on CD56Dim NK cell phenotype for untreated MS patients (p-value 0.031) and treated MS patients (p-value 0.036). We report altered calcium mobilisation in CD56Bright NK cells and to a lesser extent CD56Dim NK cells between healthy controls, treated and untreated MS patients. Conclusion: This investigation suggests variations in TRPM3 expression and calcium mobilisation of NK cells may be implicated in the pathogenesis of MS. Further investigation is required to determine the mechanism by which alemtuzumab alters calcium signaling in NK cells.
基金funded by Coordination for the Improvement of Higher Education Personnel (CAPES,Brazil-Finance Code 001,to LRB)the S?o Paulo Research Foundation(FAPESP,Brazil,project#2018/07366-4)+1 种基金The National Council for Scientific and Technological Development (CNPq,Brazil,project#303006/2018-8,to LRB)a PhD fellowship from FAPESP under Grant Agreement No 2020/02109-3。
文摘The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating mechanism is dependent on reactive oxygen species. In pathological conditions, transient receptor potential melastatin 2 is overactivated, leading to a Ca~(2+) influx that alters cell homeostasis and promotes cell death. The role of transient receptor potential melastatin 2 in neurodegenerative diseases, including Alzheimer's disease and ischemia, has already been described and reviewed. However, data on transient receptor potential melastatin 2 involvement in Parkinson's disease pathology has emerged only in recent years and the issue lacks review studies that focus specifically on this topic. The present review aims to elucidate the role of the transient receptor potential melastatin 2 channel in Parkinson's disease by reviewing, summarizing, and discussing the in vitro, in vivo, and human studies published until August 2022. Here we describe fourteen studies that evaluated the transient receptor potential melastatin 2 channel in Parkinson's disease. The Parkinson's disease model used, transient receptor potential melastatin 2 antagonist and genetic approaches, and the main outcomes reported were discussed. The studies described transient receptor potential melastatin 2 activation and enhanced expression in different Parkinson's disease models. They also evidenced protective and restorative effects when using transient receptor potential melastatin 2 antagonists, knockout, or silencing. This review provides a literature overview and suggests where there is a need for more research. As a perspective point, this review shows evidence that supports transient receptor potential melastatin 2 as a pharmacological target for Parkinson's disease in the future.
文摘Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling condition of unknown cause having multi-system manifestations. Our group has investigated the potential role of transient receptor potential (TRP) ion channels in the etiology and pathomechanism of this illness. Store-operated calcium entry (SOCE) signaling is the primary intracellular calcium signaling mechanism in non-excitable cells and is associated with TRP ion channels. While the sub-family (Canonical) TRPC has been traditionally associated with this important cellular mechanism, a member of the TRPM sub-family group (Melastatin), TRPM3, has also been recently identified as participating in SOCE in white matter of the central nervous system. We have identified single nucleotide polymorphisms (SNPs) in TRP genes in natural killer (NK) cells and peripheral blood mononuclear cells (PBMCs) in CFS/ME patients. We also describe biochemical pathway changes and calcium signaling perturbations in blood cells from patients. The ubiquitous distribution of TRP ion channels and specific locations of sub-family group members such as TRPM3 suggest a contribution to systemic pathology in CFS/ME.
文摘目的探讨TRPC3基因多态性与原发性高血压患者左心室肥厚(LVH)的关系。方法305例原发性高血压患者根据左心室质量指数(LVMI)分为单纯高血压224例(对照组)和高血压合并LVH 81例(LVH组)。分析2组年龄、吸烟史等一般资料差异。留取外周血标本,采用Sequenom MassARRAY®SNP检测技术对TRPC3基因单核苷酸多态性(SNP)位点Rs2292232、Rs4995894、Rs4292355进行基因分型。Logistic回归分析影响患者LVH的因素。结果(1)2组年龄、吸烟史、饮酒史、家族史、尿素、肌酐、空腹血糖、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、24 h平均舒张压(24 h DBP)差异无统计学意义(P>0.05),LVH组较对照组男性比例降低,而24 h平均收缩压(24 h SBP)、体质量指数(BMI)升高(P<0.05)。(2)2组Rs4995894及Rs4292355位点等位基因频率、基因型频率分布差异无统计学意义(P>0.05),TRPC3基因SNP位点Rs2292232基因型频率和等位基因频率分布差异有统计学意义(P<0.05),其中LVH组Rs2292232位点TT基因型频率较对照组更高(P<0.05)。(3)Logistic回归分析显示,女性(OR=0.332,95%CI:0.181~0.610)、较高24 h SBP(OR=1.035,95%CI:1.014~1.056)、TRPC3基因SNP Rs2292232 TT基因型(OR=2.105,95%CI:1.109~3.995)为原发性高血压患者发生LVH的独立危险因素(均P<0.05)。结论TRPC3基因Rs2292232位点SNP与高血压患者发生LVH有关,其中TT基因型患者更易发生LVH。
文摘目的探讨经典瞬时受体电位通道蛋白3(TRPC3)与脑源性神经营养因子(BDNF)在阿尔茨海默病(AD)大鼠模型海马组织中的表达及其相互关系。方法将SD大鼠随机分为PBS组、AD组和AD+BDNF组。采用β-淀粉样蛋白(Aβ1-42)侧脑室注射,制备AD模型。BDNF在造模14 d后经侧脑室导管注入。Morris水迷宫实验测定大鼠的空间学习记忆能力。实时PCR和Western blotting分别检测海马组织中TRPC3和BDNF m RNA和蛋白的表达情况。结果 Morris水迷宫实验表明,AD组大鼠第5天逃避潜伏期较PBS组延长(P<0.05);AD+BDNF组大鼠的逃避潜伏期较AD组缩短(P<0.05)。实时PCR及Western blotting结果表明,与PBS组相比,TRPC3和BDNF m RNA和蛋白在AD组表达均降低(P<0.05);与AD组相比,TRPC3 m RNA和蛋白在AD+BDNF组表达均增高(P<0.05)。结论 BDNF和TRPC3在AD大鼠海马组织表达降低;外源性BDNF可能通过上调TRPC3表达,从而改善Aβ1-42导致的AD大鼠空间学习记忆障碍,起到保护神经元的作用。
