Role of connexin-43 hemichannels in the pathogenesis of Yersinia enterocolitica.
Connexin (Cx) channels are sites of cytoplasmic communication between contacting cells. Evidence indicates that the opening of hemichannels occurs under both physiological and pathological conditions. In this paper, the involvement of Cx-43 hemichannels is demonstrated in the pathogenesis of Yersinia. Parental HeLa cells and transfected HeLa cells stably expressing Cx-43 (HCx43) were infected with Yersiniaenterocolitica, and bacterial uptake was measured by the colony-forming unit method. Bacterial uptake was higher in HCx43 cells than in parental cells and was inhibited by the Cx channel blocker, 18-alpha-glycyrrhetinic acid (AGA). The inhibitory effect of AGA was more pronounced on the Y. enterocolitica uptake by HCx43 cells than by parental cells. The ability of HCx43 cells to incorporate the permeable fluorescent tracer Lucifer Yellow (LY) was assessed. Dye incorporation was inhibited by AGA, whereas Y. enterocolitica infection of HCx43 cells increased LY incorporation. Western blotting analysis demonstrated that Y. enterocolitica infection of HCx43 cells induced tyrosine phosphorylation of Cx-43, thus supporting a critical role for Cx-43 in the strategies exploited by bacterial pathogens to invade non-phagocytic cells.
Velasquez Almonacid
L A
LA
Dipartimento di Patologia e Sanità Animale, Università di Napoli Federico II, via F. Delpino 1, 80137 Napoli, Italy.
Tafuri
S
S
Dipineto
L
L
Matteoli
G
G
Fiorillo
E
E
Della Morte
R
R
Fioretti
A
A
Menna
L F
LF
Staiano
N
N
D000818:Animals; D001422:Bacterial Adhesion; D015169:Colony Count, Microbial; D018031:Connexin 43 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007546:Isoquinolines / Q000378:metabolism; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism; D015008:Yersinia enterocolitica / Q000472:pathogenicity*
D018031:Connexin 43; D007546:Isoquinolines; C119129:18alpha-glycyrrhetinic acid; D014443:Tyrosine; C017475:lucifer yellow; D006034:Glycyrrhetinic Acid