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Gap‐junction disassembly and connexin 43 dephosphorylation induced by 18β‐glycyrrhetinic acid
Author(s) -
Guan Xiaojun,
Wilson Susan,
Schlender Keith K.,
Ruch Randall J.
Publication year - 1996
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199607)16:3<157::aid-mc6>3.0.co;2-e
Subject(s) - dephosphorylation , connexin , gap junction , okadaic acid , biology , phosphorylation , microbiology and biotechnology , phosphatase , biochemistry , cell junction , cell , biophysics , intracellular
Gap‐junction channels connect the interiors of adjacent cells and can be arranged into aggregates or plaques consisting of hundreds to thousands of channel particles. The mechanism of channel aggregation into plaques and whether plaques can disaggregate are not known. Many carcinogenic and tumor‐promoting chemicals have been identified that inhibit cell‐cell gap‐junctional coupling. Here, we provide morphological evidence that 18β‐glycyrrhetinic acid (18β‐GA), a saponin isolated from licorice root that is an inhibitor of gap‐junctional communication, caused the disassembly of gap‐junction plaques in WB‐F344 rat liver epithelial cells. This effect was dose (5–40 μM) and time dependent (1–4 h treatment). Gap‐junction channels in WB‐F344 cells are comprised of connexin 43 (Cx43), and the protein is phosphorylated to a species known as Cx43‐P2 coincident with the assembly of channels into plaques. Consistent with this, the disassembly of plaques induced by 18β‐GA was correlated with decreases in Cx43‐P2 levels and increases in nonphosphorylated Cx43. Biochemical evidence indicated that these changes in the P2 and NP forms of Cx43 represented 18β‐GA‐induced dephosphorylation of Cx43‐P2 and not its degradation or the inhibition of Cx43‐NP phosphorylation. Okadaic acid and calyculin A, which are inhibitors of type 1 and type 2A protein phosphatases, prevented the dephosphorylation of Cx43, suggesting that one or both of these phosphatases were involved in Cx43 dephosphorylation. These data indicate that 18β‐GA causes type 1 or type 2A protein phosphatase‐mediated Cx43 dephosphorylation coincident with the disassembly of gap‐junction plaques. © 1996 Wiley‐Liss, Inc.