Melatonin Protects Against Endometriosis via Regulation of Matrix Metalloproteinase-3 and an Apoptotic Pathway.
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Melatonin Protects Against Endometriosis via Regulation of Matrix Metalloproteinase-3 and an Apoptotic Pathway.
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| Creator |
Paul, Sumit
Bhattacharya, Partha Das Mahapatra, Pramathes Swarnakar, Snehasikta |
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| Subject |
Drug Development/Diagnostics & Biotechnology
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| Description |
The role of matrix metalloproteinases (MMPs) in endometriosis, a
gynecological disease of women, is unclear. The study investigated the
activity of MMP-3 and its interplay with MMP-9 during the onset of
endometriosis. Additionally, the importance of MMP-3 on the apoptotic
pathway in endometriosis and effect of melatonin thereon were investigated.
A Significant increase in the activity of MMP-3 with the severity of
endometriosis in human was observed which was found similar in mice also.
During the early phase of endometriosis, MMP-3 but not MMP-9 was
increased and associated with the expression of transcription factor, c-Fos.
Moreover, urokinase plasminogen activator and tissue inhibitor of
metalloproteinase (TIMP)-3 were involved in MMP-3 regulation during
endometriosis. Furthermore, MMP-3 activity that was parallel to c-Fos
expression in endometriosis was reduced by melatonin pretreatment as
characterized by diminished activator protein (AP)-1 DNA-binding activity.
Because decreased apoptosis is an explanation for the perpetuation of
endometriosis, we tested the role of melatonin on apoptotic pathway in
preventing endometriosis. Significant regression of glandular epithelium was
observed in melatonin-treated when compared to untreated mice. Melatonin
treatment increased apoptotic cells in endometriotic zones. This was related
to reduced Bcl-2 expression along with increased Bax expression and
caspase-9 activation. In summary, early induction of MMP-3 was distinct
from MMP-9 during endometriosis, which was regulated by c-Fos and
TIMP-3. Melatonin suppressed MMP-3 activity and amplified apoptosis
while regressing endometriosis through a caspase-3 mediated pathway. Thus,
melatonin may be a therapeutic agent for resolving endometriosis.
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| Publisher |
Blackwell Publishing
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| Date |
2010
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/84/1/JOURNAL_OF_PINEAL_RESEARCH_49(2)156%2D168;2010[39].pdf
Paul, Sumit and Bhattacharya, Partha and Das Mahapatra, Pramathes and Swarnakar, Snehasikta (2010) Melatonin Protects Against Endometriosis via Regulation of Matrix Metalloproteinase-3 and an Apoptotic Pathway. Journal Of Pineal Research, 49. pp. 156-168. |
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| Relation |
http://dx.doi.org/10.1111/j.1600-079X.2010.00780.x
http://www.eprints.iicb.res.in/84/ |
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