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Stimulation of fibroblast proliferation by neokyotorphin requires Ca 2+ influx and activation of PKA, CaMK II and MAPK/ERK
Author(s) -
Sazonova Olga V.,
Blishchenko Elena Yu.,
Tolmazova Anna G.,
Khachin Dmitry P.,
Leontiev Konstantin V.,
Karelin Andrey A.,
Ivanov Vadim T.
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05594.x
Subject(s) - bisindolylmaleimide , protein kinase c , activator (genetics) , protein kinase a , staurosporine , chemistry , kinase , mapk/erk pathway , phorbol , microbiology and biotechnology , endocrinology , medicine , biochemistry , biology , receptor
Neokyotorphin [TSKYR, hemoglobin α‐chain fragment (137–141)] has previously been shown to enhance fibroblast proliferation, its effect depending on cell density and serum level. Here we show the dependence of the effect of neokyotorphin on cell type and its correlation with the effect of protein kinase A (PKA) activator 8‐Br‐cAMP, but not the PKC activator 4β‐phorbol 12‐myristate, 13‐acetate (PMA). In L929 fibroblasts, the proliferative effect of neokyotorphin was suppressed by the Ca 2+ L ‐type channel inhibitors verapamil or nifedipine, the intracellular Ca 2+ chelator 1,2‐bis(2‐aminophenoxy)ethane‐ N , N , N ′, N ′ ‐ tetraacetic acid acetoxymethyl ester, kinase inhibitors H‐89 (PKA), KN‐62 (Ca 2+ /calmodulin‐dependent kinase II) and PD98059 (mitogen‐activated protein kinase). The proliferative effect of 8‐Br‐cAMP was also suppressed by KN‐62 and PD98059. PKC suppression (downregulation with PMA or inhibition with bisindolylmaleimide XI) did not affect neokyotorphin action. The results obtained point to a cAMP‐like action for neokyotorphin.