Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Collateral spread of apoptosis to nearby cells is referred to as the bystander effect, a process that is integral to tissue homeostasis and a challenge to anticancer therapies. In many systems, apoptosis relies on permeabilization of the mitochondrial outer membrane to factors such as cytochrome c and Smac/DIABLO. This permeabilization occurs via formation of a mitochondrial apoptosis-induced channel (MAC) and was mimicked here by single-cell microinjection of cytochrome c into Xenopus laevis embryos. Waves of apoptosis were observed in vivo from the injected to the neighboring cells. This finding indicates that a death signal generated downstream of cytochrome c release diffused to neighboring cells and ultimately killed the animals. The role of MAC in bystander effects was then assessed in mouse embryonic fibroblasts that did or did not express its main components, Bax and/or Bak. Exogenous expression of green fluorescent protein-Bax triggered permeabilization of the outer membrane and apoptosis in these cells. Time-lapse videos showed that neighboring cells also underwent apoptosis, but expression of Bax and/or Bak was essential to this effect, because no bystanders were observed in cells lacking both of these MAC components. These results may guide development of novel therapeutic strategies to selectively eliminate tumors or minimize the size of tissue injury in degenerative or traumatic cell death.
Adams,
The Bcl-2 protein family: arbiters of cell survival.
1998, Pubmed
Adams,
The Bcl-2 protein family: arbiters of cell survival.
1998,
Pubmed Burdak-Rothkamm,
ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells.
2007,
Pubmed Carter,
Loss of XChk1 function triggers apoptosis after the midblastula transition in Xenopus laevis embryos.
2003,
Pubmed
,
Xenbase Carter,
Cyclin A1/Cdk2 is sufficient but not required for the induction of apoptosis in early Xenopus laevis embryos.
2006,
Pubmed
,
Xenbase Chipuk,
Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis.
2004,
Pubmed Cory,
The Bcl-2 family: roles in cell survival and oncogenesis.
2003,
Pubmed Cotrina,
Astrocytic gap junctions remain open during ischemic conditions.
1998,
Pubmed Cusato,
Gap junctions remain open during cytochrome c-induced cell death: relationship of conductance to 'bystander' cell killing.
2006,
Pubmed
,
Xenbase Cusato,
Gap junctions mediate bystander cell death in developing retina.
2003,
Pubmed Cusato,
An experimental approach to the study of gap-junction-mediated cell death.
2003,
Pubmed
,
Xenbase Danial,
Cell death: critical control points.
2004,
Pubmed Das,
The nuclear receptor interacting factor-3 transcriptional coregulator mediates rapid apoptosis in breast cancer cells through direct and bystander-mediated events.
2007,
Pubmed Dejean,
Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel.
2005,
Pubmed Dejean,
Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?
2006,
Pubmed Finkielstein,
The midblastula transition in Xenopus embryos activates multiple pathways to prevent apoptosis in response to DNA damage.
2001,
Pubmed
,
Xenbase Guo,
Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC.
2004,
Pubmed Guthrie,
Patterns of junctional communication during development of the early amphibian embryo.
1988,
Pubmed
,
Xenbase Johnson,
Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring.
2010,
Pubmed
,
Xenbase Khodjakov,
Laser micro-irradiation of mitochondria: is there an amplified mitochondrial death signal in neural cells?
2004,
Pubmed Kinnally,
A tale of two mitochondrial channels, MAC and PTP, in apoptosis.
2007,
Pubmed Koturbash,
Irradiation induces DNA damage and modulates epigenetic effectors in distant bystander tissue in vivo.
2006,
Pubmed Kroemer,
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009.
2009,
Pubmed Krutovskikh,
Gap junction intercellular communication propagates cell death in cancerous cells.
2002,
Pubmed Landesman,
Gap junctional communication in the early Xenopus embryo.
2000,
Pubmed
,
Xenbase Li,
Cell-specific induction of apoptosis by microinjection of cytochrome c. Bcl-xL has activity independent of cytochrome c release.
1997,
Pubmed Lin,
Gap-junction-mediated propagation and amplification of cell injury.
1998,
Pubmed Martinez-Caballero,
Some amphiphilic cations block the mitochondrial apoptosis-induced channel, MAC.
2004,
Pubmed Martinez-Caballero,
Assembly of the mitochondrial apoptosis-induced channel, MAC.
2009,
Pubmed Martinez-Caballero,
The role of the mitochondrial apoptosis induced channel MAC in cytochrome c release.
2005,
Pubmed Pavlov,
A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast.
2001,
Pubmed Peixoto,
MAC inhibitors suppress mitochondrial apoptosis.
2009,
Pubmed Peixoto,
Mitochondrial apoptosis is amplified through gap junctions.
2009,
Pubmed Ryu,
Role of mitochondrial ion channels in cell death.
2010,
Pubmed Sedelnikova,
DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models.
2007,
Pubmed Wei,
Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death.
2001,
Pubmed Wroble,
Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis.
2005,
Pubmed
,
Xenbase Yang,
Preventing retinal detachment-associated photoreceptor cell loss in Bax-deficient mice.
2004,
Pubmed Zhivotovsky,
Injected cytochrome c induces apoptosis.
1998,
Pubmed
