Coleman ML, Sahai EA, Yeo M, Bosch M, Dewar A and Olson MFMembrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat. Cell Biol. 3: 339-345

Institute of Cancer Research, Londinium, England, United Kingdom
Nature Cell Biology (Impact Factor: 19.68). 05/2001; 3(4):339-45. DOI: 10.1038/35070009
Source: PubMed


The execution phase of apoptosis is characterized by marked changes in cell morphology that include contraction and membrane blebbing. The actin-myosin system has been proposed to be the source of contractile force that drives bleb formation, although the biochemical pathway that promotes actin-myosin contractility during apoptosis has not been identified. Here we show that the Rho effector protein ROCK I, which contributes to phosphorylation of myosin light-chains, myosin ATPase activity and coupling of actin-myosin filaments to the plasma membrane, is cleaved during apoptosis to generate a truncated active form. The activity of ROCK proteins is both necessary and sufficient for formation of membrane blebs and for re-localization of fragmented DNA into blebs and apoptotic bodies.

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    • "Considering that TNF-α is known to induce the disruption of actin cytoskeleton in endothelial cells [29] [30] and that the disruption of actin cytoskeleton is tightly related with the release of membrane vesicles [7] [31], it is possible that TNF-α activation caused the enlargement of the spaces among cytoskeletal filaments due to the local relaxation/ disruption of actin cytoskeleton and that some cytoplasmic matters were squeezed out through the enlarged spaces during air drying to form the particle-like structures. Taken together, our data indicate that cell-bound membrane vesicles are hemisphere-shaped and that the actin cortical network lies at the cytosolic opening of a vesicle instead of being closely attached to the inner side of the vesicle membrane. "
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    Biochimica et Biophysica Acta (BBA) - Biomembranes 07/2015; 1848(10):2225-2232. DOI:10.1016/j.bbamem.2015.06.025 · 3.84 Impact Factor
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    • "ROS may act as an initiatorin this process by cleaving poly ADP-Ribose polymerase (PARP), the 70 KD protein of the U1-ribonucleoprotein and a subunit of the DNA dependent protein kinase [34], [35]. The ROS activated caspase-3 cleaves PARP at the amino acid motif site DEVD triggering apoptosis [33], [36], [37]. Inhibition of these processes was in turn inferred to reduce cell death, and EPO was successfully used in this study in demonstrating significant reductions in the levels of ROS and caspase-3 activation in H9C2 cells upon exposure to H/R. "
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    ABSTRACT: Hypoxia/Reoxygenation (H/R) cardiac injury is of great importance in understanding Myocardial Infarctions, which affect a major part of the working population causing debilitating side effects and often-premature mortality. H/R injury primarily consists of apoptotic and necrotic death of cardiomyocytes due to a compromise in the integrity of the mitochondrial membrane. Major factors associated in the deregulation of the membrane include fluctuating reactive oxygen species (ROS), deregulation of mitochondrial permeability transport pore (MPTP), uncontrolled calcium (Ca2+) fluxes, and abnormal caspase-3 activity. Erythropoietin (EPO) is strongly inferred to be cardioprotective and acts by inhibiting the above-mentioned processes. Surprisingly, the underlying mechanism of EPO's action and H/R injury is yet to be fully investigated and elucidated. This study examined whether EPO maintains Ca2+ homeostasis and the mitochondrial membrane potential (ΔΨm) in cardiomyocytes when subjected to H/R injury and further explored the underlying mechanisms involved. H9C2 cells were exposed to different concentrations of EPO post-H/R, and 20 U/ml EPO was found to significantly increase cell viability by inhibiting the intracellular production of ROS and caspase-3 activity. The protective effect of EPO was abolished when H/R-induced H9C2 cells were treated with Wortmannin, an inhibitor of Akt, suggesting the mechanism of action through the activation Akt, a major survival pathway.
    PLoS ONE 09/2014; 9(9):e107453. DOI:10.1371/journal.pone.0107453 · 3.23 Impact Factor
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    • "On the other hand, they have been proposed to be an early degenerative change that develops when actin attachments between the plasma membrane of the hair cell and the underlying cytoskeleton were weakened [31]. Since these blebs were characteristically observed in this work following the use of high dose of nicotine they could be as an association with apoptotic hair cell injury as suggested by [34]. "
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