Induction of Anoikis Following Myoblast Transplantation into SCID Mouse Muscles Requires the Bit1 and FADD Pathways

Bouchentouf, Manaf; Benabdallah, Basma; Rousseau, Joël; Schwartz, Lawrence M.; Tremblay, Jacques P.

doi:10.1111/j.1600-6143.2007.01830.x

Cited by 43 publications

(39 citation statements)

References 35 publications

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“…We used HUVECs in this experiment, because normal cells are more sensitive to anoikis than tumor cells (1), and knockdown of Bit1 expression in HUVECs significantly protected cells from anoikis (data not shown), as previously demonstrated in other normal cell lines (4,6,7). Down-regulating PKD expression by siRNA greatly reduced cytosolic concentration of endogenous Bit1 (Fig.…”

Section: Pkd Knockdown Attenuates and Pkd Activation Enhances Bit1supporting

confidence: 58%

“…Upon loss of cell attachment, it is released from the mitochondria into the cytosol and promotes apoptosis. Suppression of Bit1 expression in tumor cells as well as in normal cells significantly protects cells from detachment-induced apoptosis, demonstrating a key role of Bit1 in anoikis (4,6,7). Unlike other apoptotic pathways, Bit1-induced apoptosis is uniquely controlled by integrin-mediated cell attachment.…”

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confidence: 98%

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Protein Kinase D Is a Positive Regulator of Bit1 Apoptotic Function

Biliran

Jan

Chen

et al. 2008

Journal of Biological Chemistry

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Bit1 (Bcl-2 inhibitor of transcription) is a mitochondrial protein that induces caspase-independent apoptosis upon its release into the cytoplasm. Bit1 is primarily associated with anoikis (cell death induced by detachment from the extracellular matrix), because the apoptotic function of Bit1 is inhibited by integrin-mediated cell attachment but not by many other antiapoptotic treatments. Here, we show that protein kinase D (PKD) regulates Bit1 apoptotic function. Overexpression of constitutively active PKD or PKD activation by treatment with phorbol 12-myristate 13-acetate results in phosphorylation of two serine residues (Ser 5 and Ser 87 ) in a form of Bit1 that is confined to the cytoplasm and concomitantly increases the apoptotic activity of cytoplasmic Bit1. Conversely, suppressing PKD activity with pharmacological inhibitors or small interfering RNA approaches attenuates apoptosis induced by cytoplasmic Bit1. Furthermore, PKD regulates induction of cell death by wild-type Bit1 following loss of cell attachment to the extracellular matrix. Activation of PKD enhances Bit1 function in anoikis, whereas inhibiting PKD function with pharmacological inhibitors or small interfering RNA compromises the ability of Bit1 to induce anoikis. The induction of Bit1-mediated apoptosis by PKD is in part attributable to the release of Bit1 from mitochondria to the cytoplasm as a consequence of phosphorylation of Ser 5 in the mitochondrial localization sequence of Bit1. Consistent with the regulatory role of PKD in the anoikis function of Bit1, we found that cell attachment to fibronectin inhibits PKD activity. These studies identify the PKD serine/threonine kinase as one of the signaling molecules through which integrin-mediated cell attachment controls Bit1 activity and anoikis.

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Section: Pkd Knockdown Attenuates and Pkd Activation Enhances Bit1supporting

confidence: 58%

mentioning

confidence: 98%

Protein Kinase D Is a Positive Regulator of Bit1 Apoptotic Function

Biliran

Jan

Chen

et al. 2008

Journal of Biological Chemistry

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“…Natural killer cell infiltration was in fact very scarce after myoblast transplantation in mice to play a role in the death of the grafted myoblasts [159]. Other causes suggested to induce apoptosis of the grafted myoblasts were hypoxia [141] and anoikis [160]. However, experiments trying to control each of the previous factors in mice never prevented the whole cell death, and only minimal enhancements of survival were reported [152,[161][162][163][164].…”

Section: The Early Survival Of the Myogenic Cellsmentioning

confidence: 99%

Cell Transplantation and “Stem Cell Therapy” in the Treatment of Myopathies: Many Promises in Mice, Few Realities in Humans

Skuk

2013

ISRN Transplantation

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Myopathies produce deficits in skeletal muscle function and, in some cases, progressive and irreversible loss of skeletal muscles. The transplantation of myogenic cells, that is, cells able to differentiate into myofibers, is an experimental strategy for the potential treatment of some of these diseases. The objectives pursued by the transplantation of these cells are essentially three: (a) the fusion with the patient's myofibers to obtain the expression of therapeutic proteins into them, (b) the neoformation of new functional myofibers in skeletal muscles that were too degenerated by the progressive degeneration, and (c) the formation of a new pool of healthy donor-derived satellite cells. Although the repertoire of myogenic cells appears to have expanded in recent years, myoblasts are the only cells that have been demonstrated to engraft in humans. The present work aims to make a comprehensive review of the subject, from its beginnings to recent advances, including the preclinical experience in different animal models and recent clinical findings.

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“…Thus, MGF-Ct24E could protect cells from apoptosis induced by other factors, which use different pathways. It has been reported that transplanted myoblast death is caused by inflammatory reaction, anoikis and hypoxia (52)(53)(54). These factors induce apoptosis of injected cells by triggering cytokine receptors, such as TNFR-1, as well as apoptotic proteins like Bit-1 and FADD.…”

Section: An Mgf E Peptide Improves Myoblast Transplantation Figure 2:mentioning

confidence: 99%

A Synthetic Mechano Growth Factor E Peptide Enhances Myogenic Precursor Cell Transplantation Success

Mills

Dominique

Lafrenière

et al. 2007

American Journal of Transplantation

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Myogenic precursor cell (MPC) transplantation is a good strategy to introduce dystrophin expression in muscles of Duchenne muscular dystrophy (DMD) patients. Insulin-like growth factor (IGF-1) promotes MPC activities, such as survival, proliferation, migration and differentiation, which could enhance the success of their transplantation. Alternative splicing of the IGF-1 mRNA produces different muscle isoforms. The mechano growth factor (MGF) is an isoform, especially expressed after a mechanical stress. A 24 amino acids peptide corresponding to the C-terminal part of the MGF E domain (MGF-Ct24E peptide) was synthesized. This peptide had been shown to enhance the proliferation and delay the terminal differentiation of C 2 C 12 myoblasts. The present study showed that the MGFCt24E peptide improved human MPC transplantation by modulating their proliferation and differentiation. Indeed, intramuscular or systemic delivery of this synthetic peptide significantly promoted engraftment of human MPCs in mice. In vitro experiments demonstrated that the MGF-Ct24E peptide enhanced MPC proliferation by a different mechanism than the binding to the IGF-1 receptor. Moreover, MGF-Ct24E peptide delayed human MPC differentiation while having no outcome on survival. Those combined effects are probably responsible for the enhanced transplantation success. Thus, the MGF-Ct24E peptide is an interesting agent to increase MPC transplantation success in DMD patients.

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Induction of Anoikis Following Myoblast Transplantation into SCID Mouse Muscles Requires the Bit1 and FADD Pathways

Cited by 43 publications

References 35 publications

Protein Kinase D Is a Positive Regulator of Bit1 Apoptotic Function

Protein Kinase D Is a Positive Regulator of Bit1 Apoptotic Function

Cell Transplantation and “Stem Cell Therapy” in the Treatment of Myopathies: Many Promises in Mice, Few Realities in Humans

A Synthetic Mechano Growth Factor E Peptide Enhances Myogenic Precursor Cell Transplantation Success

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