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Melatonin‐induced calbindin‐D9k expression reduces hydrogen peroxide‐mediated cell death in rat pituitary GH3 cells
Author(s) -
Yoo YeongMin,
Jeung EuiBae
Publication year - 2010
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2009.00730.x
Subject(s) - melatonin , programmed cell death , gene knockdown , endocrinology , medicine , biology , apoptosis , oxidative stress , protein kinase a , kinase , microbiology and biotechnology , biochemistry
In this study, we investigated whether calbindin‐D9k (CaBP‐9k) expression was regulated by melatonin during hydrogen peroxide (H 2 O 2 )‐induced cell death in rat pituitary GH3 cells. CaBP‐9k expression was increased by melatonin in a dose‐ and time‐dependent manner, indicating that CaBP‐9k expression is regulated by melatonin. Cell survival was increased approximately 27–30% where H 2 O 2 ‐treated cells (0.25 or 0.5 m m ) were also incubated with 1 m m melatonin, when compared with H 2 O 2 alone or H 2 O 2 plus 0.5 m m melatonin. This result was consistent with 4,6‐diamidino‐2‐phenylindole staining. CaBP‐9k expression was also augmented by co‐treatment with H 2 O 2 and 1 m m melatonin, suggesting a functional relationship between increased cell death and melatonin‐induced CaBP‐9k expression during H 2 O 2 ‐mediated apoptosis. Bcl‐2‐associated protein expression increased following treatment with H 2 O 2 alone, whereas Bcl‐2 expression was elevated following treatment with melatonin alone, or H 2 O 2 plus melatonin. The expression of p53 was depressed by treatment with melatonin alone, or co‐treatment with H 2 O 2 plus melatonin. These results correlated with CaBP‐9k expression levels and activation of the mitogen‐activated protein kinase/extracellular signal‐regulated kinase signaling pathway. Knockdown of CaBP‐9k expression using a small inhibitory RNA resulted in an elevation of H 2 O 2 ‐induced cell death, whereas cell survival was increased in cells that overexpressed CaBP‐9k, providing additional evidence that the induction of CaBP‐9k expression may be associated with survival signaling during H 2 O 2 ‐mediated oxidative cell death. CaBP‐9k appears to interact with p53, suggesting a possible role for this interaction in cell proliferation and cell cycle progression.