Latrunculin B modulates electrophysiological characteristics and arrhythmogenesis in pulmonary vein cardiomyocytes

2016 ◽  
Vol 130 (9) ◽  
pp. 721-732 ◽  
Author(s):  
Yen-Yu Lu ◽  
Yung-Kuo Lin ◽  
Zhi-Hong Wen ◽  
Yao-Chang Chen ◽  
Shih-Ann Chen ◽  
...  
Keyword(s):  
Pulmonary Vein ◽  
Actin Polymerization ◽  
Latrunculin B

Lat-B inhibits actin polymerization and Ca2+regulation. Lat-B regulates PV electrophysiology and Ca2+ homeostasis. Lat-B may attenuate PV-initiated AF during stretch.

Anti-HLA-DR Monoclonal Antibody Evokes a Novel Non-Apoptotic Cell Death Pathway In Acute Lymphoblastic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3245-3245
Author(s):  
Khimara Naidoo ◽  
Waleed Alduaij ◽  
Jamie Honeychurch ◽  
Eleanor Cheadle ◽  
Seema Alexander ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Lines ◽  
Actin Polymerization ◽  
Lymphoblastic Leukemia ◽  
Cell Contact ◽  
Latrunculin B ◽  
Hla Dr

Abstract Abstract 3245 Whilst modern treatment approaches cure a high number of patients with acute lymphoblastic leukemia (ALL), little progress has been made in the treatment of refractory and relapsed ALL and new treatment approaches are needed. We recently demonstrated that anti-HLA-DR class II monoclonal antibody (mAb) L243 induces a novel non-apoptotic mode of cell death in B-cell lymphoma lines, defined by homotypic adhesion (HA), actin reorganisation and lysosomal activity (Ivanov et al. J Clin Invest, 2009). Here, we extend these important observations and examine whether this novel form of mAb induced cell death occurs in pre-B ALL cell lines. Expression of HLA-DR was determined using flow cytometry in a panel of ALL cell lines (REH, SupB15 and SD1). HLA-DR was expressed at high levels on each of the cell lines. The ability of L243 to induce HA and cell death (Annexin V/PI positivity) was assessed using microscopy and flow cytometry respectively. L243 was able to evoke both strong HA and cell death in all of the ALL cell lines (e.g. in SupB15 cells 46±1.7% death versus 7±0.5% in controls, p<0.001 by Student's t-test). Inhibitors of actin polymerization (cytochalasin D, latrunculin B) were used to assess the role of actin in cell death and HA induced by L243. These inhibitors of actin polymerization inhibited both HA and cell death elicited by L243 (e.g. in SupB15 cells 24±0.5% death versus 10.3±0.8% with Latrunculin B, p<0.001), demonstrating the dependence of HA and cell death on actin reorganisation. The importance of cell to cell contact in this form of antibody induced cell death was confirmed by the addition of low-melting point agarose which physically blocked cell to cell contact and markedly attenuated cell death induced by L243. In contrast using the pan-caspase inhibitor QVD OPH had no effect on cell death induced by L243, indicating that this mode of death is non-apoptotic. These findings demonstrate that anti-HLA DR mAb L243 induces a novel model of cell death in ALL cell lines that is independent of caspase activation and dependent on actin reorganization. This data suggests that this novel mAb induced death pathway is independent of apoptosis and potentially exploitable in the clinic in leukemias resistant to chemotherapy apoptosis induction. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Actin depolymerization is sufficient to induce programmed cell death in self-incompatible pollen

2006 ◽  
Vol 174 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Steven G. Thomas ◽  
Shanjin Huang ◽  
Shutian Li ◽  
Christopher J. Staiger ◽  
Vernonica E. Franklin-Tong
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Actin Polymerization ◽  
Caspase 3 ◽  
Tip Growth ◽  
Causal Link ◽  
Actin Dynamics ◽  
Latrunculin B ◽  
Actin Depolymerization ◽  
Incompatible Pollen

Self-incompatibility (SI) prevents inbreeding through specific recognition and rejection of incompatible pollen. In incompatible Papaver rhoeas pollen, SI triggers a Ca2+ signaling cascade, resulting in the inhibition of tip growth, actin depolymerization, and programmed cell death (PCD). We investigated whether actin dynamics were implicated in regulating PCD. Using the actin-stabilizing and depolymerizing drugs jasplakinolide (Jasp) and latrunculin B, we demonstrate that changes in actin filament levels or dynamics play a functional role in initiating PCD in P. rhoeas pollen, triggering a caspase-3–like activity. Significantly, SI-induced PCD in incompatible pollen was alleviated by pretreatment with Jasp. This represents the first account of a specific causal link between actin polymerization status and initiation of PCD in a plant cell and significantly advances our understanding of the mechanisms involved in SI.

scholarly journals Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5648
Author(s):  
Jei-Ming Peng ◽  
Wei-Yu Chen ◽  
Jai-Hong Cheng ◽  
Jia-Wun Luo ◽  
Hong-Tai Tzeng
Keyword(s):  
Cell Adhesion ◽  
Focal Adhesion ◽  
Actin Polymerization ◽  
Cell Detachment ◽  
Latrunculin B ◽  
Adhesion Protein ◽  
Initial Tumor ◽  
Cytoskeleton Remodeling ◽  
Focal Adhesion Protein ◽  
Tgf Β1

Detachment of cancer cells is the first step in tumor metastasis and malignancy. However, studies on the balance of initial tumor anchoring and detachment are limited. Herein, we revealed that the regulation of cytoskeleton proteins potentiates tumor detachment. The blockage of TGF-β1 using neutralizing antibodies induced cancer cell detachment in the Boyden chamber and 3D in-gel spheroid models. Moreover, treatment with latrunculin B, an actin polymerization inhibitor, enhanced cell dissociation by abolishing actin fibers, indicating that TGF-β1 mediates the formation of actin stress fibers, and is likely responsible for the dynamics of anchoring and detachment. Indeed, latrunculin B disrupted the formation of external TGF-β1-induced actin fibers and translocation of intracellular vinculin, a focal adhesion protein, resulting in the suppression of cell adhesion. Moreover, the silencing of vimentin substantially reduced cell adhesion and enhanced cell detachment, revealing that cell adhesion and focal adhesion protein translocation stimulated by TGF-β1 require vimentin. Using the 3D in-gel spheroid model, we found that latrunculin B suppressed the cell adhesion promoted by external TGF-β1, increasing the number of cells that penetrated the Matrigel and detached from the tumor spheres. Thus, cytoskeleton remodeling maintained the balance of cell anchoring and detachment, and the TGF-β1/vimentin/focal adhesion protein assembly axis was involved in the control dynamics of initial tumor detachment.

scholarly journals Differential display proteomic analysis ofPicea meyeripollen germination and pollen-tube growth after inhibition of actin polymerization by latrunculin B

2006 ◽  
Vol 47 (2) ◽  
pp. 174-195 ◽  
Author(s):  
Yanmei Chen ◽  
Tong Chen ◽  
Shihua Shen ◽  
Maozhong Zheng ◽  
Yiming Guo ◽  
...  
Keyword(s):  
Pollen Tube ◽  
Differential Display ◽  
Pollen Tube Growth ◽  
Proteomic Analysis ◽  
Actin Polymerization ◽  
Tube Growth ◽  
Latrunculin B

Hypertonic inhibition of exocytosis in neutrophils: central role for osmotic actin skeleton remodeling

2000 ◽  
Vol 279 (3) ◽  
pp. C619-C633 ◽  
Author(s):  
Sandro B. Rizoli ◽  
Ori D. Rotstein ◽  
Jean Parodo ◽  
M. James Phillips ◽  
Andras Kapus
Keyword(s):  
Osmotic Stress ◽  
Signaling Pathways ◽  
Causal Relationship ◽  
Tyrosine Phosphorylation ◽  
Actin Polymerization ◽  
Actin Assembly ◽  
Latrunculin B ◽  
Actin Ring ◽  
Twofold Increase ◽  
Cytoskeletal Remodeling

Hypertonicity suppresses neutrophil functions by unknown mechanisms. We investigated whether osmotically induced cytoskeletal changes might be related to the hypertonic inhibition of exocytosis. Hyperosmolarity abrogated the mobilization of all four granule types induced by diverse stimuli, suggesting that it blocks the process of exocytosis itself rather than individual signaling pathways. Concomitantly, osmotic stress provoked a twofold increase in F-actin, induced the formation of a submembranous F-actin ring, and abolished depolymerization that normally follows agonist-induced actin assembly. Several observations suggest a causal relationship between actin polymerization and inhibition of exocytosis: 1) prestimulus actin levels were inversely proportional to the stimulus-induced degranulation, 2) latrunculin B (LB) prevented the osmotic actin response and restored exocytosis, and 3) actin polymerization induced by jasplakinolide inhibited exocytosis under isotonic conditions. The shrinkage-induced tyrosine phosphorylation and the activation of the Na+/H+exchanger were not affected by LB. Inhibition of osmosensitive kinases failed to prevent the F-actin change, suggesting that the osmotic tyrosine phosphorylation and actin polymerization are independent phenomena. Thus cytoskeletal remodeling appears to be a key component in the neutrophil-suppressive, anti-inflammatory effects of hypertonicity.

scholarly journals Stretch-induced contractile differentiation of vascular smooth muscle: sensitivity to actin polymerization inhibitors

2003 ◽  
Vol 284 (6) ◽  
pp. C1387-C1396 ◽  
Author(s):  
Asad Zeidan ◽  
Ina Nordström ◽  
Sebastian Albinsson ◽  
Ulf Malmqvist ◽  
Karl Swärd ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Actin Polymerization ◽  
Cytochalasin D ◽  
Latrunculin B ◽  
Rhoa Activity ◽  
Mechanical Compliance ◽  
Tissue Compliance ◽  
Portal Veins ◽  
Endogenous Release

Signaling mechanisms for stretch-dependent growth and differentiation of vascular smooth muscle were investigated in mechanically loaded rat portal veins in organ culture. Stretch-dependent protein synthesis was found to depend on endogenous release of angiotensin II. Autoradiography after [35S]methionine incorporation revealed stretch-dependent synthesis of several proteins, of which SM22 and actin were particularly prominent. Inhibition of RhoA activity by cell-permeant C3 toxin increased tissue mechanical compliance and reduced stretch-dependent extracellular signal-regulated kinase (ERK)1/2 activation, growth, and synthesis of actin and SM22, suggesting a role of the actin cytoskeleton. In contrast, inhibition of Rho-associated kinase by Y-27632 did not reduce ERK1/2 phosphorylation or actin and SM22 synthesis and did not affect tissue mechanical compliance but still inhibited overall growth. The actin polymerization inhibitors latrunculin B and cytochalasin D both inhibited growth and caused increased tissue compliance. Whereas latrunculin B concentration-dependently reduced actin and SM22 synthesis, cytochalasin D did so at low (10−8M) but not at high (10−6M) concentration. The results show that stretch stabilizes the contractile smooth muscle phenotype. Stretch-dependent differentiation marker expression requires an intact cytoskeleton for stretch sensing, control of protein expression via the level of unpolymerized G-actin, or both.

scholarly journals BEX1 and BEX4 Induce GBM Progression through Regulation of Actin Polymerization and Activation of YAP/TAZ Signaling

2021 ◽  
Vol 22 (18) ◽  
pp. 9845
Author(s):  
Sungmin Lee ◽  
Hyunkoo Kang ◽  
Eunguk Shin ◽  
Jaewan Jeon ◽  
HyeSook Youn ◽  
...  
Keyword(s):  
Mouse Model ◽  
Glial Cells ◽  
Poor Prognosis ◽  
Actin Polymerization ◽  
Tumor Formation ◽  
High Grade ◽  
Latrunculin B ◽  
Xenograft Mouse Model ◽  
Orthotopic Xenograft ◽  
Radiation Induced

GBM is a high-grade cancer that originates from glial cells and has a poor prognosis. Although a combination of surgery, radiotherapy, and chemotherapy is prescribed to patients, GBM is highly resistant to therapies, and surviving cells show increased aggressiveness. In this study, we investigated the molecular mechanism underlying GBM progression after radiotherapy by establishing a GBM orthotopic xenograft mouse model. Based on transcriptomic analysis, we found that the expression of BEX1 and BEX4 was upregulated in GBM cells surviving radiotherapy. We also found that upregulated expression of BEX1 and BEX4 was involved in the formation of the filamentous cytoskeleton and altered mechanotransduction, which resulted in the activation of the YAP/TAZ signaling pathway. BEX1- and BEX4-mediated YAP/TAZ activation enhanced the tumor formation, growth, and radioresistance of GBM cells. Additionally, latrunculin B inhibited GBM progression after radiotherapy by suppressing actin polymerization in an orthotopic xenograft mouse model. Taken together, we suggest the involvement of cytoskeleton formation in radiation-induced GBM progression and latrunculin B as a GBM radiosensitizer.

scholarly journals Actin Polymerization Is Essential for Pollen Tube Growth

2001 ◽  
Vol 12 (8) ◽  
pp. 2534-2545 ◽  
Author(s):  
Luis Vidali ◽  
Sylvester T. McKenna ◽  
Peter K. Hepler
Keyword(s):  
Pollen Tube ◽  
Pollen Tube Growth ◽  
Cytoplasmic Streaming ◽  
Actin Polymerization ◽  
Tip Growth ◽  
Dnase I ◽  
Tube Growth ◽  
Similar Proportion ◽  
Latrunculin B ◽  
Inhibition Of Growth

Actin microfilaments, which are prominent in pollen tubes, have been implicated in the growth process; however, their mechanism of action is not well understood. In the present work we have used profilin and DNAse I injections, as well as latrunculin B and cytochalasin D treatments, under quantitatively controlled conditions, to perturb actin microfilament structure and assembly in an attempt to answer this question. We found that a ∼50% increase in the total profilin pool was necessary to half-maximally inhibit pollen tube growth, whereas a ∼100% increase was necessary for half-maximal inhibition of cytoplasmic streaming. DNAse I showed a similar inhibitory activity but with a threefold more pronounced effect on growth than streaming. Latrunculin B, at only 1–4 nM in the growth medium, has a similar proportion of inhibition of growth over streaming to that of profilin. The fact that tip growth is more sensitive than streaming to the inhibitory substances and that there is no correlation between streaming and growth rates suggests that tip growth requires actin assembly in a process independent of cytoplasmic streaming.

scholarly journals Gα11 Signaling through ARF6 Regulates F-Actin Mobilization and GLUT4 Glucose Transporter Translocation to the Plasma Membrane

2001 ◽  
Vol 21 (15) ◽  
pp. 5262-5275 ◽  
Author(s):  
Avirup Bose ◽  
Andrew D. Cherniack ◽  
Stephen E. Langille ◽  
Sarah M. C. Nicoloro ◽  
Joanne M. Buxton ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Actin Polymerization ◽  
Glucose Transporter ◽  
Kinase Inhibitor ◽  
Active Form ◽  
Glut4 Translocation ◽  
Phosphatidylinositol 3 Kinase ◽  
Cortical Actin ◽  
Latrunculin B ◽  
Endothelin 1

ABSTRACT The action of insulin to recruit the intracellular GLUT4 glucose transporter to the plasma membrane of 3T3-L1 adipocytes is mimicked by endothelin 1, which signals through trimeric Gαq or Gα11 proteins. Here we report that murine Gα11 is most abundant in fat and that expression of the constitutively active form of Gα11 [Gα11(Q209L)] in 3T3-L1 adipocytes causes recruitment of GLUT4 to the plasma membrane and stimulation of 2-deoxyglucose uptake. In contrast to the action of insulin on GLUT4, the effects of endothelin 1 and Gα11 were not inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin at 100 nM. Signaling by insulin, endothelin 1, or Gα11(Q209L) also mobilized cortical F-actin in cultured adipocytes. Importantly, GLUT4 translocation caused by all three agents was blocked upon disassembly of F-actin by latrunculin B, suggesting that the F-actin polymerization caused by these agents may be required for their effects on GLUT4. Remarkably, expression of a dominant inhibitory form of the actin-regulatory GTPase ARF6 [ARF6(T27N)] in cultured adipocytes selectively inhibited both F-actin formation and GLUT4 translocation in response to endothelin 1 but not insulin. These data indicate that ARF6 is a required downstream element in endothelin 1 signaling through Gα11 to regulate cortical actin and GLUT4 translocation in cultured adipocytes, while insulin action involves different signaling pathways.

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