PHOSOLAMBAN AND CAM KINASE II IN STOMACH SMOOTH MUSCLE PLASTICITY

福索兰班和 CAM 激酶 II 在胃平滑肌可塑性中的作用

• 批准号: 8168459
• 负责人: Brian A Perrino
• 金额: $ 21.07万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168459
• 关键词: Activities of Daily Living; Agonist; Biological Assay; Cell Volumes; Characteristics; Colon; Computer Retrieval of Information on Scientific Projects Database; Contractile Proteins; Defect; Disease; Exhibits; Fractionation; Frequencies; Funding; Fundus; Gastrointestinal tract structure; Genetic Transcription; Grant; Holoenzymes; Hypertrophy; Image; In Situ Hybridization; Institution; Lead; Maps; Mechanics; Molecular; Muscle Contraction; Nuclear Localization Signal; Obstruction; Pathology; Pattern; Phosphopeptides; Phosphorylation; Phosphotransferases; Physiological; Physiology; Property; Proteomics; RNA Splicing; Regulation; Research; Research Personnel; Resources; Role; Serum Response Factor; Smooth Muscle; Source; Stomach; Therapeutic; Tissues; Translating; United States National Institutes of Health; Variant; Western Blotting; calmodulin-dependent protein kinase II; cell motility; gastrointestinal; motility disorder; muscle hypertrophy; ratiometric; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Gastrointestinal smooth muscles adapt contractile activities in response to continuously changing conditions. Mechanical plasticity, such as hypertrophy, alters the functional capacity of smooth muscles in response to changing demands by reorganizing contractile bundles. The amplitude and frequency of cytosolic Ca 2+ oscillations encodes information that is translated into physiological responses. CaM kinase II has the structural, catalytic, and regulatory properties required of a molecular decoder of Ca 2+ oscillations. Fundus and colon smooth muscles, which exhibit distinct Ca 2+oscillations, express CaM kinase II holoenzymes with tissue-specific enzymatic properties. In situ hybridization, kinase assays, Western blotting, and ratiometric Ca 2+ imaging will be used to investigate how CaM kinase II responds to cytosolic Ca 2+ transients in order to understand how it modulates smooth muscle contractile activity. Hypertrophy of gastrointestinal smooth muscles due to obstructions of the digestive tract resulting from congenital or acquired defects is associated with pathologies that lead to several motility disorders. Part of the cell volume increase results from elevated transcription and expression of contractile proteins under the control of serum response factor. Serum response factor is activated by CaM kinase II phosphorylation. Fundus and colon smooth muscles express CaM kinase II splice variants containing a nuclear localization signal. Cellular fractionation, Western blotting, kinase assays, Q-PCR, phosphopeptide mapping, and expression proteomics will be used to elucidate the role of CaM kinase II in the activation of contractile protein gene transcription by serum response factor. Gastrointestinal smooth muscle hypertrophy is important in normal physiology and disease. This project will explore the regulation and physiological roles of CaM kinase II in normal agonist-stimulated, and abnormal hypertrophied gastrointestinal smooth muscles. Determining the enzymatic characteristics of gastrointestinal smooth muscle CaM kinase II and investigating the modulation of gastrointestinal smooth muscle contraction by CaM kinase II will provide additional information for developing better therapeutics aimed at treating the myogenic component of the altered motility patterns that underlie digestive tract motility disorders.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 胃肠平滑肌适应收缩活动，以应对不断变化的条件。 机械可塑性，如肥大，改变平滑肌的功能能力，以响应 通过重组收缩束来改变需求。胞浆Ca ~（2+）的振幅和频率 振荡将信息编码成生理反应。CaM激酶II具有 结构，催化和调节性能所需的分子解码器的钙2+振荡。眼底 和结肠平滑肌，表现出明显的钙振荡，表达钙调蛋白激酶II全酶， 组织特异性酶特性。原位杂交、激酶测定、蛋白质印迹和比率测定 钙离子成像将用于研究钙调素激酶II如何响应胞浆钙离子瞬变，以 了解它如何调节平滑肌收缩活动。胃肠平滑肌肥大 由于先天性或后天性缺陷导致的消化道阻塞导致的肌肉 导致几种运动障碍的病理。细胞体积增加的部分原因是 收缩蛋白的转录和表达受血清反应因子的控制。血清 反应因子被CaM激酶II磷酸化激活。胃底和结肠平滑肌表达 含有核定位信号的CaM激酶II剪接变体。细胞分级分离，蛋白质印迹， 激酶测定、Q-PCR、磷酸肽图谱和表达蛋白质组学将用于阐明 CaM激酶II在血清反应因子激活收缩蛋白基因转录中的作用 胃肠平滑肌肥大在正常生理和疾病中是重要的。该项目将 探讨钙调素激酶II在正常激动剂刺激和异常激动剂刺激中的调节和生理作用。 肥大的胃肠平滑肌。测定胃肠道的酶特性 平滑肌钙调素激酶II和研究胃肠平滑肌收缩的调节 将为开发更好的治疗方法提供额外的信息， 肌原性成分的改变运动模式的基础消化道运动障碍。