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Up-Regulation
of Gap Junctional Intercellular Communication by Hexamethylene Bisacetamide
in Cultured Human Peritoneal Mesothelial Cells |
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Takahiko Ogawa,
Tomonori Hayashi, Seishi Kyoizumi, Takafumi Ito, James E. Trosko, and Noriaki
Yorioka |
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Department
of Internal Medicine (TO), Hiroshima Prefectural Hospital, Department of
Radiobiology (TO, TH, SK), Radiation Effects Research Foundation, Second
Department of Internal Medicine (TI, NY), Hiroshima University School of
Medicine, Hiroshima, Japan; and Department of Pediatrics/Human Development
(JET), Michigan State University, East Lansing, Michigan |
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SUMMARY: Gap junctional
intercellular communication (GJIC) is believed to be an important means
of regulating cell growth and the malignant potential of tumors. This study
examined the effect of hexamethylene bisacetamide (HMBA), a hybrid polar
compound and a potent differentiation inducer, on GJIC in cultured primary
human peritoneal mesothelial cells. The redistribution of fluorescence after
photobleaching was used to detect GJIC. After the incubation of confluent
cell cultures with 3 or 6 mM HMBA for 3 and 6 days, GJIC was significantly
increased in a concentration-dependent manner compared with cultures without
HMBA. Western blotting showed that connexin 43 (Cx43), the major functional
protein of gap junctions in peritoneal mesothelial cells, was present in
unphosphorylated and phosphorylated forms in control cell cultures. The
addition of HMBA to cultures induced a significant increase of total Cx43
protein because of an increase of the phosphorylated forms. Immunofluorescence
studies showed that HMBA increased the intensity of fluorescence for Cx43
at cell membrane borders. Quantitative reverse transcription and PCR analysis
revealed that the addition of HMBA to cultures resulted in the concentration-dependent
up-regulation of mRNA for Cx43. These results indicate that HMBA induces
the enhancement of GJIC in peritoneal mesothelial cells through both the
up-regulation of Cx43 messages and an increase of post-translational phosphorylation.
HMBA may contribute to the maintenance of cellular homeostasis through the
up-regulation of GJIC. |
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