Adenoviral delivery of human connexin37 induces endothelial cell death through apoptosis.
Gap junction channels formed of connexins directly link the cytoplasm of adjacent cells and have been implicated in intercellular signaling that may regulate the functions of vascular cells. To facilitate connexin manipulation and analysis of their roles in adult endothelial cells, we developed adenoviruses containing the vascular connexins (Cx37, Cx40, and Cx43). We infected cultured human umbilical vein endothelial cells with control or connexin adenoviruses. Connexin expression was verified by immunoblotting and immunofluorescence. Infection with the Cx37 adenovirus (but not control or other connexin adenoviruses) led to a dose-dependent death of the endothelial cells that was partially antagonized by the gap junction blocker alpha-glycyrrhetinic acid and altered the intercellular transfer of Lucifer yellow and neurobiotin. Cell morphology, Annexin V and TUNEL staining, and caspase 3 assays all implicated apoptosis in the cell death. These data suggest that connexin-specific alterations of intercellular communication may modulate endothelial cell growth and death.
Seul
Kyung H
KH
Section of Pediatric Hematology/Oncology and Stem Cell Transplantation, University of Chicago, Chicago, IL 60637-1470, USA.
Kang
Keum Y
KY
Lee
Kyung S
KS
Kim
Suhn H
SH
Beyer
Eric C
EC
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000235:genetics* / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D018014:Gene Transfer Techniques; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009447:Neuroblastoma; D051381:Rats; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
D018031:Connexin 43; D017630:Connexins; D006034:Glycyrrhetinic Acid; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein; C119129:18alpha-glycyrrhetinic acid