subject:(blebbistatin)

San Jose State University

1. Eng, Wilson S. Nonlinear Stiffness and Viscoelasticity of Inhibitor-Treated Blood Clots by Tensile Testing.

Degree: MS, Mechanical Engineering, 2018, San Jose State University

URL: https://doi.org/10.31979/etd.8rjd-8389 ; https://scholarworks.sjsu.edu/etd_theses/4964

► Although blood clots are vital to wound healing, little is known about what factors influence clot stiffness and dynamic response. This work investigates the… (more)

Subjects/Keywords: Blebbistatin; Blood clots; Cytochalasin; Nonlinear stiffness; Tensile testing; Viscoelasticity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Eng, W. S. (2018). Nonlinear Stiffness and Viscoelasticity of Inhibitor-Treated Blood Clots by Tensile Testing. (Masters Thesis). San Jose State University. Retrieved from https://doi.org/10.31979/etd.8rjd-8389 ; https://scholarworks.sjsu.edu/etd_theses/4964

Chicago Manual of Style (16^th Edition):

Eng, Wilson S. “Nonlinear Stiffness and Viscoelasticity of Inhibitor-Treated Blood Clots by Tensile Testing.” 2018. Masters Thesis, San Jose State University. Accessed January 20, 2021. https://doi.org/10.31979/etd.8rjd-8389 ; https://scholarworks.sjsu.edu/etd_theses/4964.

MLA Handbook (7^th Edition):

Eng, Wilson S. “Nonlinear Stiffness and Viscoelasticity of Inhibitor-Treated Blood Clots by Tensile Testing.” 2018. Web. 20 Jan 2021.

Vancouver:

Eng WS. Nonlinear Stiffness and Viscoelasticity of Inhibitor-Treated Blood Clots by Tensile Testing. [Internet] [Masters thesis]. San Jose State University; 2018. [cited 2021 Jan 20]. Available from: https://doi.org/10.31979/etd.8rjd-8389 ; https://scholarworks.sjsu.edu/etd_theses/4964.

Council of Science Editors:

Eng WS. Nonlinear Stiffness and Viscoelasticity of Inhibitor-Treated Blood Clots by Tensile Testing. [Masters Thesis]. San Jose State University; 2018. Available from: https://doi.org/10.31979/etd.8rjd-8389 ; https://scholarworks.sjsu.edu/etd_theses/4964

2. 河田, 晋一. ミオシンII阻害薬 (2,3-Butanedione monoxime) がモルモット盲腸紐平滑筋スキンド標本弛緩過程に及ぼす影響 : Effect of myosin II inhibitors (2,3-Butanedione monoxime) on the relaxation process of skinned taenia cecum smooth muscle from guinea pig.

Degree: 修士（健康科学）, 2016, Tokyo Metropolitan University / 首都大学東京

URL: http://hdl.handle.net/10748/7737

►

2,3-Butanedione monoxime (BDM)は、ミオシンII阻害薬としてミオシン・アクチン相互作用を直接的に阻害することにより、骨格筋収縮を可逆的に抑制することが知られている。また、BDMは平滑筋収縮も阻害するが、その作用機序は、ミオシン・アクチン相互作用阻害に起因するというよりは、細胞内 Ca^<2+>濃度上昇の抑制によるものと考えられてきた (Lang RJ, Paul RJ: J Physiol, 433: 1-24, 1991) 。最近、別のミオシンII阻害薬blebbistatinが、ミオシン・アクチン相互作用を直接的に阻害することで、平滑筋収縮抑制および弛緩促進を惹起することが報告された。(Watanabe: J Physiol Sci, 62: S160, 2012.)。本研究では、平滑筋のミオシン・アクチン相互作用に対するBDMの影響の詳細を明らかにする目的で、細胞膜を化学的に破壊したモルモット盲腸紐平滑筋スキンド標本を用いて、その弛緩過程に対するBDMの影響を2つの温度条件で検討した。BDMは、10mM以下では平滑筋弛緩過程に影響を及ぼさなかったが、30mMで弛緩を促進させた。弛緩時間過程の解析から、BDMは速い活性化クロスブリッジの解離を促進させることで、弛緩を促進させることが示唆された。

2,3-Butanedione monoxime (BDM) is known… (more)

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2,3-Butanedione monoxime (BDM)は、ミオシンII阻害薬としてミオシン・アクチン相互作用を直接的に阻害することにより、骨格筋収縮を可逆的に抑制することが知られている。また、BDMは平滑筋収縮も阻害するが、その作用機序は、ミオシン・アクチン相互作用阻害に起因するというよりは、細胞内 Ca^<2+>濃度上昇の抑制によるものと考えられてきた (Lang RJ, Paul RJ: J Physiol, 433: 1-24, 1991) 。最近、別のミオシンII阻害薬blebbistatinが、ミオシン・アクチン相互作用を直接的に阻害することで、平滑筋収縮抑制および弛緩促進を惹起することが報告された。(Watanabe: J Physiol Sci, 62: S160, 2012.)。本研究では、平滑筋のミオシン・アクチン相互作用に対するBDMの影響の詳細を明らかにする目的で、細胞膜を化学的に破壊したモルモット盲腸紐平滑筋スキンド標本を用いて、その弛緩過程に対するBDMの影響を2つの温度条件で検討した。BDMは、10mM以下では平滑筋弛緩過程に影響を及ぼさなかったが、30mMで弛緩を促進させた。弛緩時間過程の解析から、BDMは速い活性化クロスブリッジの解離を促進させることで、弛緩を促進させることが示唆された。

2,3-Butanedione monoxime (BDM) is known as a myosin II inhibitor, reversibly suppressing skeletal muscle contraction by direct inhibition of myosin-actin interaction. BDM also inhibits smooth muscle contraction, but the mechanism of the force suppression has been thought to interfere with intracellular Ca2+ handling rather than that with myosin-actin interaction. Recently, it has been reported that blebbistatin, another myosin II inhibitor, induced suppression of contraction and acceleration of relaxation in smooth muscle by direct inhibition of myosin-actin interaction. To investigate the effects of BDM on the myosin-actin interaction in smooth muscle in detail, the present study aimed to examine BDM effects on the relaxation process of cell membrane permeabilized (skinned) taenia cecum from guinea pig under two different experimental (temperature) conditions. BDM did not affect relaxation time courses at 10 mM or lower, but accelerated the relaxation at 30 mM. Analysis of the relaxation time course suggests that BDM accelerated dissociation of fast-cycling cross-bridge, inducing rapid tension decay during relaxation.

首都大学東京, 2016-03-25, 修士（健康科学）

Subjects/Keywords: 平滑筋; 2,3-Butanedione monoxime (BDM); blebbistatin; ミオシン・アクチン相互作用

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

河田, �. (2016). ミオシンII阻害薬 (2,3-Butanedione monoxime) がモルモット盲腸紐平滑筋スキンド標本弛緩過程に及ぼす影響 : Effect of myosin II inhibitors (2,3-Butanedione monoxime) on the relaxation process of skinned taenia cecum smooth muscle from guinea pig. (Thesis). Tokyo Metropolitan University / 首都大学東京. Retrieved from http://hdl.handle.net/10748/7737

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

河田, 晋一. “ミオシンII阻害薬 (2,3-Butanedione monoxime) がモルモット盲腸紐平滑筋スキンド標本弛緩過程に及ぼす影響 : Effect of myosin II inhibitors (2,3-Butanedione monoxime) on the relaxation process of skinned taenia cecum smooth muscle from guinea pig.” 2016. Thesis, Tokyo Metropolitan University / 首都大学東京. Accessed January 20, 2021. http://hdl.handle.net/10748/7737.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

河田, 晋一. “ミオシンII阻害薬 (2,3-Butanedione monoxime) がモルモット盲腸紐平滑筋スキンド標本弛緩過程に及ぼす影響 : Effect of myosin II inhibitors (2,3-Butanedione monoxime) on the relaxation process of skinned taenia cecum smooth muscle from guinea pig.” 2016. Web. 20 Jan 2021.

Vancouver:

河田 �. ミオシンII阻害薬 (2,3-Butanedione monoxime) がモルモット盲腸紐平滑筋スキンド標本弛緩過程に及ぼす影響 : Effect of myosin II inhibitors (2,3-Butanedione monoxime) on the relaxation process of skinned taenia cecum smooth muscle from guinea pig. [Internet] [Thesis]. Tokyo Metropolitan University / 首都大学東京; 2016. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10748/7737.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

河田 �. ミオシンII阻害薬 (2,3-Butanedione monoxime) がモルモット盲腸紐平滑筋スキンド標本弛緩過程に及ぼす影響 : Effect of myosin II inhibitors (2,3-Butanedione monoxime) on the relaxation process of skinned taenia cecum smooth muscle from guinea pig. [Thesis]. Tokyo Metropolitan University / 首都大学東京; 2016. Available from: http://hdl.handle.net/10748/7737

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. 三橋, 里子. Blebbistatinによる気管平滑筋スキンド標本弛緩促進作用のメカニズム : Mechanisms of accelerating effect of blebbistatin on relaxation process of skinned tracheal smooth muscle.

Degree: 修士（健康科学）, 2017, Tokyo Metropolitan University / 首都大学東京

URL: http://hdl.handle.net/10748/00009633

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[緒言] ミオシンII阻害薬であるblebbiststinは、平滑筋アクトミオシンATPase活性を10μM程度で抑制する。blebbistatinは平滑筋標本においては収縮のCa^<2+>感受性やミオシン軽鎖リン酸化レベルには影響は与えず、アクチン・ミオシン相互作用を直接抑制することにより、その収縮を抑制するといわれている。blebbistatinはミオシンATPase加水分解サイクルに伴うミオシンのアクチンへの結合・解離に影響を及ぼすことが考えられることから、弛緩過程におけるクロスブリッジの解離にも影響を与えることが推察される。そこで本研究では、細胞膜を化学的に破壊して気管平滑筋スキンド標本のCa^<2+>収縮後の弛緩過程とミオシンATPaseサイクルの影響を受けないrigor形成・解離に対するblebbistatinの効果を動力学的に検討した。[方法] モルモット気管平滑筋に100μMのβ-escinで処理をしてスキンド標本を作製し、圧トランスデューサーに取り付けて等尺性張力を測定した。Ca^<2+>による最大収縮の後、EGTAによりCa^<2+>を素早く除去して弛緩させ、同時にblebbistatinを添加し15分間計測した。また、Ca^<2+>収縮後のrigor状態におけるblebbistatinについても同様の方法で検討した。統計処理はt-testを使用しP＜0.05を有意水準とした。[結果] Ca^<2+>収縮後の弛緩過程において、気管平滑筋スキンド標本は30μM程度で弛緩過程を促進し、回帰分析の結果からラッチの解離を速めていた。一方、Ca^<2+>収縮後のrigor状態では相対張力において有意な弛緩はみられなかったが、回帰分析の結果、30μMでrigorの解離の抑制と収縮後一度外れたクロスブリッジがrigorに移行する割合がコントロール群と比較して少ない値を示した。[考察] Blebbistatinは、ATPやアクチンのミオシンへの結合を直接阻害するのではなく、ミオシン頭部構造変化に影響してアクチン・ミオシン結合を弱めることが知られている。ATPの有無によって、Ca^<2+>収縮で発生した収縮張力のCa^<2+>除去後の減衰過程に対するblebbistatinの影響が異なるのは、blebbistatinがミオシン頭部構造変化に与える効果はミオシン頭部へのATPの結合の有無によって変化することを強く示唆する。平滑筋細胞において無酸素状態における力学反応の実態は不明であるが、blebbistatinはその解明に向けて研究において有用なツールになると考えられる。

Blebbistatin, an inhibitor of myosin II , has an inhibitory effect on smooth muscle actomyosin ATPase activity at around 10μM.… (more)

▼

[緒言] ミオシンII阻害薬であるblebbiststinは、平滑筋アクトミオシンATPase活性を10μM程度で抑制する。blebbistatinは平滑筋標本においては収縮のCa^<2+>感受性やミオシン軽鎖リン酸化レベルには影響は与えず、アクチン・ミオシン相互作用を直接抑制することにより、その収縮を抑制するといわれている。blebbistatinはミオシンATPase加水分解サイクルに伴うミオシンのアクチンへの結合・解離に影響を及ぼすことが考えられることから、弛緩過程におけるクロスブリッジの解離にも影響を与えることが推察される。そこで本研究では、細胞膜を化学的に破壊して気管平滑筋スキンド標本のCa^<2+>収縮後の弛緩過程とミオシンATPaseサイクルの影響を受けないrigor形成・解離に対するblebbistatinの効果を動力学的に検討した。[方法] モルモット気管平滑筋に100μMのβ-escinで処理をしてスキンド標本を作製し、圧トランスデューサーに取り付けて等尺性張力を測定した。Ca^<2+>による最大収縮の後、EGTAによりCa^<2+>を素早く除去して弛緩させ、同時にblebbistatinを添加し15分間計測した。また、Ca^<2+>収縮後のrigor状態におけるblebbistatinについても同様の方法で検討した。統計処理はt-testを使用しP＜0.05を有意水準とした。[結果] Ca^<2+>収縮後の弛緩過程において、気管平滑筋スキンド標本は30μM程度で弛緩過程を促進し、回帰分析の結果からラッチの解離を速めていた。一方、Ca^<2+>収縮後のrigor状態では相対張力において有意な弛緩はみられなかったが、回帰分析の結果、30μMでrigorの解離の抑制と収縮後一度外れたクロスブリッジがrigorに移行する割合がコントロール群と比較して少ない値を示した。[考察] Blebbistatinは、ATPやアクチンのミオシンへの結合を直接阻害するのではなく、ミオシン頭部構造変化に影響してアクチン・ミオシン結合を弱めることが知られている。ATPの有無によって、Ca^<2+>収縮で発生した収縮張力のCa^<2+>除去後の減衰過程に対するblebbistatinの影響が異なるのは、blebbistatinがミオシン頭部構造変化に与える効果はミオシン頭部へのATPの結合の有無によって変化することを強く示唆する。平滑筋細胞において無酸素状態における力学反応の実態は不明であるが、blebbistatinはその解明に向けて研究において有用なツールになると考えられる。

Blebbistatin, an inhibitor of myosin II , has an inhibitory effect on smooth muscle actomyosin ATPase activity at around 10μM. Blebbistatin is also known to suppress the smooth contraction by direct inhibition of myosin-actin interaction without any effects on Ca^<2+> sensitivity to the force or phosphorylation level of myosin light chain. In the present study, to assess the blebbistatin effects on actin-myosin interaction in detail, we investigated effect of blebbistatin in the relaxation process and the reducing rigor tension after the Ca^<2+>-induced contraction using with skinned tracheal smooth muscle kinetically. A tracheal muscle preparation skinned (cell membrane permeabilized) with 100μM β-escin was attached to a force transducer to measure tension mechanical force. After contractile force induced with 10μM Ca^<2+> reached a steady level, Ca^<2+> was quickly removed in the absence or presence of ATP, resulting in relaxation process or reducing rigor tension respectively, with or without blebbistatin for 15 min. The relaxation process after the Ca^<2+>-removal was accelerated in the presence of 30μM blebbistatin and this effect of blebbistatin seemed to result from acceleration of detach from so called “latch” state. On the other hand, blebbistatin at 301M accelerated detachment of rigor bridge and reduced the forming rigor bridges in the absence of ATP, although the agent did not significantly changes in the tension level during decrease in the rigor tension after Ca^<2+> removal. The difference of the blebbistatin effects on the force between relaxation process and reducing rigor tension seems to be due to distinct effects of the agent on conformational changes of myosin in the absence and presence of ATP, because blebbistatin is known not to directly inhibit ATP binding to myosin, but to actin binding affinity of myosin.

首都大学東京, 2017-03-25, 修士（健康科学）

Subjects/Keywords: 気道平滑筋; ラッチ; ブレビスタチン; アクチン・ミオシン相互作用; airway smooth muscle; latch; blebbistatin; actin-myosin interaction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

三橋, �. (2017). Blebbistatinによる気管平滑筋スキンド標本弛緩促進作用のメカニズム : Mechanisms of accelerating effect of blebbistatin on relaxation process of skinned tracheal smooth muscle. (Thesis). Tokyo Metropolitan University / 首都大学東京. Retrieved from http://hdl.handle.net/10748/00009633

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

三橋, 里子. “Blebbistatinによる気管平滑筋スキンド標本弛緩促進作用のメカニズム : Mechanisms of accelerating effect of blebbistatin on relaxation process of skinned tracheal smooth muscle.” 2017. Thesis, Tokyo Metropolitan University / 首都大学東京. Accessed January 20, 2021. http://hdl.handle.net/10748/00009633.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

三橋, 里子. “Blebbistatinによる気管平滑筋スキンド標本弛緩促進作用のメカニズム : Mechanisms of accelerating effect of blebbistatin on relaxation process of skinned tracheal smooth muscle.” 2017. Web. 20 Jan 2021.

Vancouver:

三橋 �. Blebbistatinによる気管平滑筋スキンド標本弛緩促進作用のメカニズム : Mechanisms of accelerating effect of blebbistatin on relaxation process of skinned tracheal smooth muscle. [Internet] [Thesis]. Tokyo Metropolitan University / 首都大学東京; 2017. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10748/00009633.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

三橋 �. Blebbistatinによる気管平滑筋スキンド標本弛緩促進作用のメカニズム : Mechanisms of accelerating effect of blebbistatin on relaxation process of skinned tracheal smooth muscle. [Thesis]. Tokyo Metropolitan University / 首都大学東京; 2017. Available from: http://hdl.handle.net/10748/00009633

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of St. Andrews

4. Lawson, Christopher Peter Abiodun Tevi. The development of novel myosin inhibitors .

Degree: 2011, University of St. Andrews

URL: http://hdl.handle.net/10023/2123

► This thesis describes a structure activity relationship (SAR) study on the recently discovered small molecule tool blebbistatin (S)-21 with particular emphasis on the development of… (more)

▼ This thesis describes a structure activity relationship (SAR) study on the recently discovered small molecule tool blebbistatin (S)-21 with particular emphasis on the development of novel synthetic protocols suitable for the rapid synthesis of libraries of blebbistatin analogues. These analogues are potentially of use as novel myosin inhibitors Chapter 1 introduces the concept of chemical biology with particular emphasis on chemical genetics. This approach has rekindled the search for new chemical tools for the investigation of biological systems. The success of blebbistatin (S)-21, which was identified in a chemical genetic study, as a research tool was also discussed. The link between several myosin classes and genetic diseases such as coeliac disease, Crohn’s disease, deafness, dermatitis, familial hypertrophic cardiomyopathy, Griscelli disease and ulcerative colitis indicate that potent inhibitors which show selectivity towards specific myosin isoforms may be of great value as tools for the study of these conditions. The plan for the SAR study around (S)-21 was outlined. Chapter 2 describes the studies undertaken to develop an efficient synthetic route to N1-alkyl analogues of (S)-21 suitable for the parallel synthesis of chemical collections. These studies culminated in the synthesis of an intermediate (S)-66 from which novel N1-alkyl analogues were synthesised. The biological evaluation of these N1-alkyl analogues was discussed. Chapter 3 describes the development of a protocol suitable for the parallel synthesis of collections of N1-aryl analogues of (S)-21 via the intermediate 66. The application of this protocol to the synthesis of a collection of racemic N1-aryl and heteroaryl analogues of (S)-21 and their biological evaluation was presented. Chapter 4 describes the successful rational design and synthesis of a novel fused thiophene ring containing inhibitor of myosin II. The structure of this compound was proposed by modelling of the existing co-crystal structure of (S)-21 bound to the metastable state of Dictyostelium discoideum myosin II (S1dC) and sought to optimise the π-π stacking interaction displayed by (S)-21 with the tyrosine 261 residue within its binding site. The biological evaluation of this novel analogue was discussed. In Chapter 5 the studies conducted to investigate the contribution of ring-C to the binding affinity of (S)-21 were described. The development of alternate routes to (S)-21, in an attempt to avoid difficulties experienced during the synthesis of some analogues of (S)-21, are described. The synthesis and biological investigation of the fluorescent dye PPBA whose binding site has been suggested to overlap with that of (S)-21 was also reported. Advisors/Committee Members: Westwood, Nicholas James (advisor).

Subjects/Keywords: Blebbistatin; Myosin; Inhibitor; Small molecule tool; Coupling reactions; Heterocycles; Amidines; Guanidines; Cytokenesis; Motor domain; Stereoisomerism; Molecular models

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lawson, C. P. A. T. (2011). The development of novel myosin inhibitors . (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/2123

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lawson, Christopher Peter Abiodun Tevi. “The development of novel myosin inhibitors .” 2011. Thesis, University of St. Andrews. Accessed January 20, 2021. http://hdl.handle.net/10023/2123.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lawson, Christopher Peter Abiodun Tevi. “The development of novel myosin inhibitors .” 2011. Web. 20 Jan 2021.

Vancouver:

Lawson CPAT. The development of novel myosin inhibitors . [Internet] [Thesis]. University of St. Andrews; 2011. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10023/2123.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lawson CPAT. The development of novel myosin inhibitors . [Thesis]. University of St. Andrews; 2011. Available from: http://hdl.handle.net/10023/2123

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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