TY - JOUR
T1 - Gap junctions remain open during cytochrome c-induced cell death
T2 - Relationship of conductance to 'bystander' cell killing
AU - Cusato, K.
AU - Ripps, H.
AU - Zakevicius, J.
AU - Spray, D. C.
N1 - Funding Information:
This work was supported by the NIH Grants HL07675 (KC); EY-06516, EY-01792 and EY-14557 (HR); MH-65495 (DCS), a Grass Foundation Fellowship (KC), an unrestricted award to the UIC Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness Inc., a Senior Research Investigator Award from RPB (HR), and an Award of Merit from the Alcon Research Institute (HR). We thank Dr. Julie Schnapf for helpful discussions.
PY - 2006/10
Y1 - 2006/10
N2 - Previous reports have shown that gap junctions relay cell death in many cell types. However, changes in electrical coupling and their dynamics during cell death are poorly understood. We performed comprehensive studies of electrical coupling following induction of cell death by single-cell cytochrome c (cyC) injection in paired Xenopus oocytes. Cell death was rapidly induced by cyC in injected cells, and cell death was also observed in uninjected bystander cells electrically coupled to the cyC-injected oocytes. Gap junction currents either remained at pre-cyC injection levels or increased dramatically as the injected cell died. Nonjunctional currents increased in injected cells immediately following cyC injection; nonjunctional currents increased slowly in uninjected bystander cells. Bystander cell death occurred only when junctional conductance was ∼6 μS. Both 1,2-bis-(o-aminophenoxy)-ethane-N,N,-N′,N′-tetraacetic acid tetraacetoxy-methyl ester and Xestospongin C inhibited bystander cell death in pairs that had reached the death conductance threshold, suggesting that Ca2+ and inositol 1,4,5 triphosphate are involved in the process.
AB - Previous reports have shown that gap junctions relay cell death in many cell types. However, changes in electrical coupling and their dynamics during cell death are poorly understood. We performed comprehensive studies of electrical coupling following induction of cell death by single-cell cytochrome c (cyC) injection in paired Xenopus oocytes. Cell death was rapidly induced by cyC in injected cells, and cell death was also observed in uninjected bystander cells electrically coupled to the cyC-injected oocytes. Gap junction currents either remained at pre-cyC injection levels or increased dramatically as the injected cell died. Nonjunctional currents increased in injected cells immediately following cyC injection; nonjunctional currents increased slowly in uninjected bystander cells. Bystander cell death occurred only when junctional conductance was ∼6 μS. Both 1,2-bis-(o-aminophenoxy)-ethane-N,N,-N′,N′-tetraacetic acid tetraacetoxy-methyl ester and Xestospongin C inhibited bystander cell death in pairs that had reached the death conductance threshold, suggesting that Ca2+ and inositol 1,4,5 triphosphate are involved in the process.
KW - Bystander effect
KW - Cell death
KW - Gap junctions
KW - Intercellular communication
KW - Xenopus oocytes
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U2 - 10.1038/sj.cdd.4401876
DO - 10.1038/sj.cdd.4401876
M3 - Article
C2 - 16485029
AN - SCOPUS:33748681711
SN - 1350-9047
VL - 13
SP - 1707
EP - 1714
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 10
ER -