The steady-state expression of connexin43 is maintained by the PI3K/Akt in osteoblasts.
The gap junction protein connexin43 (Cx43) plays an important role in bone development and its homeostasis. Therefore, it is important that the Cx43 expression is kept at a high-level in bone tissues under normal conditions. To investigate the mechanism to keep Cx43 expression level, the effects of protein kinase inhibitors on the basal expression of Cx43 were examined. It was found that the specific PI3K inhibitor LY294002 significantly decreased the steady-state expression levels of Cx43 mRNA and protein in osteoblastic cell line, MC3T3-E1 cells. Furthermore, dominant-negative Akt expression reduced both Cx43 expression and gap junction activity. These results suggest an important role of PI3K/Akt in the regulation of basal Cx43 expression. A promoter assay for Cx43 and an actinomycin D chase experiment revealed that PI3K/Akt modulated Cx43 expression post-transcriptionally via mRNA stability. The present findings could provide new insights into the molecular understanding of Cx43 expression.
Bhattacharjee
Rajib
R
Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Kaneda
Makoto
M
Nakahama
Ken-ichi
K
Morita
Ikuo
I
D000818:Animals; D002450:Cell Communication / Q000235:genetics; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics*; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology; D017629:Gap Junctions / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020871:RNA Stability
D018031:Connexin 43; D005419:Flavonoids; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one