Melatonin reduces indomethacin-induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Melatonin reduces indomethacin-induced gastric mucosal cell
apoptosis by preventing mitochondrial oxidative stress and
the activation of mitochondrial pathway of apoptosis
|
|
| Creator |
Maity, Pallab
Bindu, Samik Dey, Sumanta Goyal, Manish Alam , Athar Pal, Chinmay Reiter, Russel Bandyopadhyay, Uday |
|
| Subject |
Infectious Diseases and Immunology
|
|
| Description |
Augmentation of gastric mucosal cell apoptosis due to
development of oxidative stress is one of the main pathogenic events in the
development of nonsteroidal anti-inflammatory drug (NSAID)-induced
gastropathy. Identification of a nontoxic, anti-apoptotic molecule is
warranted for therapy against NSAID-induced gastropathy. The objective of
the present study was to define the mechanism of the anti-apoptotic effect of
melatonin, a nontoxic molecule which scavenges reactive oxygen species.
Using an array of experimental approaches, we have shown that melatonin
prevents the development of mitochondrial oxidative stress and activation
of mitochondrial pathway of apoptosis induced by indomethacin (a NSAID)
in the gastric mucosa. Melatonin inhibits the important steps of
indomethacin-induced activation of mitochondrial pathway of apoptosis
such as upregulation of the expression of Bax and Bak, and the
downregulation of Bcl-2 and BclxL. Melatonin also prevents indomethacininduced
mitochondrial translocation of Bax and prevents the collapse of
mitochondrial membrane potential. Moreover, melatonin reduces
indomethacin-mediated activation of caspase-9 and caspase-3 by blocking
the release of cytochrome c and finally rescues gastric mucosal cells from
indomethacin-induced apoptosis as measured by the TUNEL assay.
Histologic studies of gastric mucosa further document that melatonin almost
completely protects against gastric damage induced by indomethacin. Thus,
melatonin has significant anti-apoptotic effects to protect gastric mucosa
from NSAID-induced apoptosis and gastropathy, which makes its use as
potential therapy against gastric damage during NSAID treatment.
|
|
| Publisher |
Blackwell Publishing
|
|
| Date |
2009
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/223/1/JOURNAL_OF_PINEAL_RESEARCH%2C46(_3)%2C_314%2D323%2C2009[84].pdf
Maity, Pallab and Bindu, Samik and Dey, Sumanta and Goyal, Manish and Alam , Athar and Pal, Chinmay and Reiter, Russel and Bandyopadhyay, Uday (2009) Melatonin reduces indomethacin-induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis. Journal Of Pineal Research, 46 (3). pp. 314-323. |
|
| Relation |
http://dx.doi.org/10.1111/j.1600-079X.2009.00663.x
http://www.eprints.iicb.res.in/223/ |
|