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
目的研究干扰瞬时受体电位通道7(TRPM7)对人肺成纤维细胞向肌成纤维细胞转化的影响。方法用转化生长因子-β1(TGF-β1)刺激人胚肺成纤维细胞WI-38和MRC-5,Western blot检测细胞平滑肌肌动蛋白(α-SMA)和胶原Ⅰ的表达,来评价细胞的转化...目的研究干扰瞬时受体电位通道7(TRPM7)对人肺成纤维细胞向肌成纤维细胞转化的影响。方法用转化生长因子-β1(TGF-β1)刺激人胚肺成纤维细胞WI-38和MRC-5,Western blot检测细胞平滑肌肌动蛋白(α-SMA)和胶原Ⅰ的表达,来评价细胞的转化。用实时聚合酶链反应(Real-time PCR)和Western blot检测细胞中TRPM7的表达。将特异性的TRPM7 si RNA转染到细胞中,并将细胞分为对照组、模型组、TRPM7 si RNA组、转染非特异性si RNA组(Scramble组)。检测转化过程中相关蛋白α-SMA、胶原Ⅰ、Smad3、p-Smad3及Smad7的表达。结果 TGF-β1(15μg/L)作用24 h后,成功诱导肺成纤维细胞转化为肌成纤维细胞。与对照组比较,模型组细胞中TRPM7 m RNA和蛋白高表达,且细胞中α-SMA、胶原Ⅰ、Smad3及p-Smad3的蛋白表达增多,Smad7表达降低,差异有统计学意义(P<0.05)。与模型组比较,TRPM7 si RNA转染组细胞TRPM7 m RNA和蛋白低表达,且α-SMA、胶原Ⅰ、Smad3及p-Smad3的表达下降,Smad7的表达升高,差异有统计学意义(P<0.05)。结论下调TRPM7可在一定程度上干预肺成纤维细胞向肌成纤维细胞转化,该作用可能与TGF-β1/Smads信号通路有关。展开更多
AIM： To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 （TRPM7） in the human gastrointestinal （GI） tract. METHODS： Conventional microel...AIM： To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 （TRPM7） in the human gastrointestinal （GI） tract. METHODS： Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajat （ICCs）. RESULTS： The human GI tract generated slow electrical waves and had ICCs which functioned as pacemak er cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB （2-aminoethoxydiphenyl borate） and La3＋, TRPM7 channel blockers, inhibited the slowwaves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION： These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the gen- eration of the slow waves.展开更多
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.
文摘目的研究干扰瞬时受体电位通道7(TRPM7)对人肺成纤维细胞向肌成纤维细胞转化的影响。方法用转化生长因子-β1(TGF-β1)刺激人胚肺成纤维细胞WI-38和MRC-5,Western blot检测细胞平滑肌肌动蛋白(α-SMA)和胶原Ⅰ的表达,来评价细胞的转化。用实时聚合酶链反应(Real-time PCR)和Western blot检测细胞中TRPM7的表达。将特异性的TRPM7 si RNA转染到细胞中,并将细胞分为对照组、模型组、TRPM7 si RNA组、转染非特异性si RNA组(Scramble组)。检测转化过程中相关蛋白α-SMA、胶原Ⅰ、Smad3、p-Smad3及Smad7的表达。结果 TGF-β1(15μg/L)作用24 h后,成功诱导肺成纤维细胞转化为肌成纤维细胞。与对照组比较,模型组细胞中TRPM7 m RNA和蛋白高表达,且细胞中α-SMA、胶原Ⅰ、Smad3及p-Smad3的蛋白表达增多,Smad7表达降低,差异有统计学意义(P<0.05)。与模型组比较,TRPM7 si RNA转染组细胞TRPM7 m RNA和蛋白低表达,且α-SMA、胶原Ⅰ、Smad3及p-Smad3的表达下降,Smad7的表达升高,差异有统计学意义(P<0.05)。结论下调TRPM7可在一定程度上干预肺成纤维细胞向肌成纤维细胞转化,该作用可能与TGF-β1/Smads信号通路有关。
基金Supported by The Creative Research Initiative Center for Bio-Artificial Muscle of the Ministry of Education,Science and Technology (MEST) in Korea
文摘AIM： To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 （TRPM7） in the human gastrointestinal （GI） tract. METHODS： Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajat （ICCs）. RESULTS： The human GI tract generated slow electrical waves and had ICCs which functioned as pacemak er cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB （2-aminoethoxydiphenyl borate） and La3＋, TRPM7 channel blockers, inhibited the slowwaves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION： These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the gen- eration of the slow waves.
