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EDTA‐induced activation of Ca‐regulated proteins in the vaginal mucosa
Author(s) -
Sang Choe Eun,
Warrier Bharat,
Soo Chun Jang,
Cheol Park Joo,
Lee Chi H.
Publication year - 2003
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.20047
Subject(s) - p38 mitogen activated protein kinases , western blot , hela , kinase , mapk/erk pathway , nitric oxide , nitric oxide synthase , mitogen activated protein kinase , microbiology and biotechnology , immunohistochemistry , cell culture , blot , calcium , nitrite , biology , biochemistry , chemistry , cell , immunology , endocrinology , gene , ecology , genetics , organic chemistry , nitrate
The effects of EDTA on the expression and topologic localization of mitogen‐activated protein (MAP) kinases (ERK, JNK, and p38), along with nitric oxide synthase (NOS), I‐KappaB, and p53 were examined to elucidate the host response provoked by the intravaginal application of a female controlled drug delivery system (FcDDS) containing a spermicidal/microbicidal agent and EDTA. Immunohistochemical and immunoblotting studies were conducted to identify and quantitate the EDTA‐inducible proteins in vaginal mucosa. The content of nitrite, which is one of the primary stable breakdown products of nitric oxide (NO), was determined to correlate the expression of NOS with NO formation in HeLa cervical carcinoma cell line. The immunohistochemical study demonstrated that the modulation of the calcium gradient by EDTA activated MAP kinases (ERK and JNK) in the rabbit vaginal mucosa. The results of Western immunoblot study demonstrated differential expression of MAP kinases (ERK and JNK) with EDTA treatment, whereas the expression of NOS and NF‐KappaB was not affected by EDTA. There was no significant difference in nitrite production in the HeLa cell line upon exposure to EDTA compared with the control, which was consistent with the results of the Western blot study. The results of this work support that the regulation of MAP kinase was affected by calcium, which is controlled by chelation activity of EDTA. The specific tissue responses exerted by the loading components of a biomaterial‐based system should be fully taken into consideration for its intravaginal application. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 159–167, 2004

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