Abstract
Preservation of the mechanosensory function of osteocytes by inhibiting their apoptosis might contribute to the beneficial effects of bisphosphonates in bone. We report herein a mechanism by which connexin43 hemichannel opening by bisphosphonates triggers the activation of the kinases Src and ERKs and promotes cell survival. Bisphosphonate-induced anti-apoptosis requires connexin channel integrity, but not gap junctions. Osteocytic cells express functional hemichannels that are opened by bisphosphonates, as demonstrated by dye uptake, regulation by established agonists and antagonists, and cell surface biotinylation. The anti-apoptotic effect of bisphosphonates depends on connexin43 expression in mouse embryonic fibroblasts and osteoblastic cells. Transfection of connexin43, but not other connexins, into connexin43 naïve cells confers de novo responsiveness to the drugs. The signal transducing property of connexin43 requires the pore-forming, as well as the C-terminal domains of the protein, the interaction of connexin43 with Src, and the activation of both Src and ERK kinases. These studies establish a role for connexin43 hemichannels in bisphosphonate action, and a novel function of connexin43 - beyond gap junction communication - in the regulation of survival signaling pathways.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 377-382 |
| Number of pages | 6 |
| Journal | Cell Adhesion and Communication |
| Volume | 8 |
| Issue number | 4-6 |
| State | Published - 2000 |
| Externally published | Yes |
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Keywords
- Apoptosis
- Bisphosphonates
- Bone
- Connexin43
- ERKs
- Src
ASJC Scopus subject areas
- Cell Biology
Cite this
Bisphosphonate-induced, hemichannel-mediated, anti-apoptosis through the Src/ERK pathway : A gap junction-independent action of connexin43. / Plotkin, Lilian; Bellido, Teresita.
In: Cell Adhesion and Communication, Vol. 8, No. 4-6, 2000, p. 377-382.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bisphosphonate-induced, hemichannel-mediated, anti-apoptosis through the Src/ERK pathway
T2 - A gap junction-independent action of connexin43
AU - Plotkin, Lilian
AU - Bellido, Teresita
PY - 2000
Y1 - 2000
N2 - Preservation of the mechanosensory function of osteocytes by inhibiting their apoptosis might contribute to the beneficial effects of bisphosphonates in bone. We report herein a mechanism by which connexin43 hemichannel opening by bisphosphonates triggers the activation of the kinases Src and ERKs and promotes cell survival. Bisphosphonate-induced anti-apoptosis requires connexin channel integrity, but not gap junctions. Osteocytic cells express functional hemichannels that are opened by bisphosphonates, as demonstrated by dye uptake, regulation by established agonists and antagonists, and cell surface biotinylation. The anti-apoptotic effect of bisphosphonates depends on connexin43 expression in mouse embryonic fibroblasts and osteoblastic cells. Transfection of connexin43, but not other connexins, into connexin43 naïve cells confers de novo responsiveness to the drugs. The signal transducing property of connexin43 requires the pore-forming, as well as the C-terminal domains of the protein, the interaction of connexin43 with Src, and the activation of both Src and ERK kinases. These studies establish a role for connexin43 hemichannels in bisphosphonate action, and a novel function of connexin43 - beyond gap junction communication - in the regulation of survival signaling pathways.
AB - Preservation of the mechanosensory function of osteocytes by inhibiting their apoptosis might contribute to the beneficial effects of bisphosphonates in bone. We report herein a mechanism by which connexin43 hemichannel opening by bisphosphonates triggers the activation of the kinases Src and ERKs and promotes cell survival. Bisphosphonate-induced anti-apoptosis requires connexin channel integrity, but not gap junctions. Osteocytic cells express functional hemichannels that are opened by bisphosphonates, as demonstrated by dye uptake, regulation by established agonists and antagonists, and cell surface biotinylation. The anti-apoptotic effect of bisphosphonates depends on connexin43 expression in mouse embryonic fibroblasts and osteoblastic cells. Transfection of connexin43, but not other connexins, into connexin43 naïve cells confers de novo responsiveness to the drugs. The signal transducing property of connexin43 requires the pore-forming, as well as the C-terminal domains of the protein, the interaction of connexin43 with Src, and the activation of both Src and ERK kinases. These studies establish a role for connexin43 hemichannels in bisphosphonate action, and a novel function of connexin43 - beyond gap junction communication - in the regulation of survival signaling pathways.
KW - Apoptosis
KW - Bisphosphonates
KW - Bone
KW - Connexin43
KW - ERKs
KW - Src
UR - http://www.scopus.com/inward/record.url?scp=33751145145&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751145145&partnerID=8YFLogxK
M3 - Article
VL - 8
SP - 377
EP - 382
JO - Cell Communication and Adhesion
JF - Cell Communication and Adhesion
SN - 1541-9061
IS - 4-6
ER -