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Apoptotic signaling of the Amblyomin‐X involves endoplasmic reticulum stress, cell cycle regulation and survival pathways
Author(s) -
Chudzinski-Tavassi Ana Marisa,
Morais Kátia Luciano Pereira,
Souza Jean Gabriel,
Simons Simone Michaela,
Berra Carolina Maria,
Lameu Claudiana
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.798.25
Subject(s) - endoplasmic reticulum , intracellular , microbiology and biotechnology , unfolded protein response , calcium in biology , apoptosis , cell cycle , biology , cyclin d1 , signal transduction , cell , chemistry , biochemistry
The Amblyomin‐X, a Kunitz‐type inhibitor obtained in a recombinant protein form, promotes apoptosis in murine renal adenocarcinoma (RENCA), decreased proteasomal activity and increased pool of poly‐ubiquitinylated proteins in some tumor cell lines, suggesting an endoplasmic reticulum (ER)‐stress, in addition to D1 cyclin expression decrease. However, the mechanistic effects of this protein are still unclear. Objective Evaluate the involvement of ER‐stress, cell cycle regulation and/or survival in tumor cells treated or not with Amblyomin‐X. Methods The genic expression was perfomed by ABI 7500 Real Time PCR System (Life Technologies) using forward and reverse specific genes primers. The intracellular calcium mobilization was measured by confocal microscope and microfluorometry. Results RENCA cells treated with Amblyomin‐X showed significant differences in genes related to ER‐stress and cell cycle regulation, as observed for caspase‐12, which showed increased expression and for mTOR, which, in turn, showed reduction in its expression. Moreover, Amblyomin‐X did not show instantly and transiently intracellular calcium mobilization, but showed increase in this intracellular ion concentration after 5h of protein treatment. Conclusion The results suggest that ER‐stress, cell cycle regulation and survival pathway proteins are involved in this process pro‐apoptotic. Supported by FAPESP