Lansoprazole Protects and Heals Gastric Mucosa from Non-steroidal Anti-inflammatory Drug (NSAID)-induced Gastropathy by Inhibiting Mitochondrial as Well as Fas-mediated Death Pathways with Concurrent Induction of Mucosal Cell Renewal
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Lansoprazole Protects and Heals Gastric Mucosa from
Non-steroidal Anti-inflammatory Drug (NSAID)-induced
Gastropathy by Inhibiting Mitochondrial as Well as
Fas-mediated Death Pathways with Concurrent Induction of
Mucosal Cell Renewal
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| Creator |
Maity, Pallab
Bindu, Samik Choubey, Vinay Alam, Athar Mitra, Kalyan Goyal, Manish Dey, Sumanta Guha, Mithu Pal, Chinmay Bandyopadhyay, Uday |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Wehave investigated the mechanism of antiapoptotic and cell
renewal effects of lansoprazole, a proton pump inhibitor, to protect
and heal gastric mucosal injury in vivo induced by indomethacin,
a non-steroidal anti-inflammatory drug (NSAID).
Lansoprazole prevents indomethacin-induced gastric damage
by blocking activation of mitochondrial and Fas pathways of
apoptosis. Lansoprazole prevents indomethacin-induced
up-regulation of proapoptotic Bax and Bak and down-regulation
of antiapoptotic Bcl-2 and BclxL to maintain the normal
proapoptotic/antiapoptotic ratio and thereby arrests indomethacin-
induced mitochondrial translocation of Bax and collapse
of mitochondrial membrane potential followed by cytochrome
c release and caspase-9 activation. Lansoprazole also
inhibits indomethacin-induced Fas-mediated mucosal cell
death by down-regulating Fas or FasL expression and inhibiting
caspase-8 activation. Lansoprazole favors mucosal cell renewal
simultaneously by stimulating gene expression of prosurvival
proliferating cell nuclear antigen, survivin, epidermal growth
factor, and basic fibroblast growth factor. The up-regulation of
Flt-1 further indicates that lansoprazole activates vascular epidermal
growth factor-mediated controlled angiogenesis to
repair gastric mucosa. Lansoprazole also stimulates the healing
of already formed ulcers induced by indomethacin. Time
course study of healing indicates that it switches off the mitochondrial
death pathway completely but not the Fas pathway.
However, lansoprazole heals mucosal lesions almost completely
after overcoming the persisting Fas pathway, probably
by favoring the prosurvival genes expression. This study thus
provides the detailed mechanism of antiapoptotic and prosurvival
effects of lansoprazole for offering gastroprotection
against indomethacin-induced gastropathy.
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| Date |
2008
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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/236/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY%2C_283(21)%2C_14391%2D14401%2C2008[83].pdf
Maity, Pallab and Bindu, Samik and Choubey, Vinay and Alam, Athar and Mitra, Kalyan and Goyal, Manish and Dey, Sumanta and Guha, Mithu and Pal, Chinmay and Bandyopadhyay, Uday (2008) Lansoprazole Protects and Heals Gastric Mucosa from Non-steroidal Anti-inflammatory Drug (NSAID)-induced Gastropathy by Inhibiting Mitochondrial as Well as Fas-mediated Death Pathways with Concurrent Induction of Mucosal Cell Renewal. The Journal of Biological Chemistry, 283 (21). pp. 14391-14401. |
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| Relation |
http://dx.doi.org/10.1074/jbc.M800414200
http://www.eprints.iicb.res.in/236/ |
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