Effect of melatonin on secreted and induced matrix metalloproteinase-9 and -2 activity during prevention of indomethacin-induced gastric ulcer

Krishnendu Ganguly, Pallab Maity, Russel J Reiter, Snehasikta Swarnakar

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) maintain the crucial role in physiological turnover of extracellular matrix (ECM) proteins in gastric tissues. However, a little is known about the relationship of MMPs with ECM degradation during gastric ulceration and ECM remodeling during healing. Our objective was to investigate the effect of melatonin (N-acetyl-5 methoxytryptamine) on the regulation of MMP-9 and MMP-2 activity during prevention of gastric ulcer. In the present study, biochemical and zymographic methods were used to analyze the mechanism of melatonin in indomethacin-induced gastric ulcer in a rat model. Our studies reveal that melatonin dose-dependently downregulates the expression and secretion of pro-MMP-9 which is induced (approximately 10-fold) during indomethacin-induced gastric ulceration. Furthermore, melatonin prevents gastric ulceration in a dose-dependent manner through upregulation (approximately two- to threefold) of both pro-MMP-2 and active MMP-2 at the level of induction as well as secretion. It also prevents gastric ulcers by blocking glutathione depletion and lipid peroxidation in cytosolic and microsomal fractions. The novel findings of this study are attributed to the attenuation of the pro-MMP-9 and increase of MMP-2 activity by pretreatment with melatonin. The finding defines one of the MMP-mediated pathways for melatonin's action in gastric ulcer.

Original languageEnglish (US)
Pages (from-to)307-315
Number of pages9
JournalJournal of Pineal Research
Volume39
Issue number3
DOIs
StatePublished - Oct 2005

Fingerprint

Secreted Matrix Metalloproteinases
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Melatonin
Stomach Ulcer
Indomethacin
Stomach
Matrix Metalloproteinases
Extracellular Matrix
5-Methoxytryptamine
Extracellular Matrix Proteins
Lipid Peroxidation
Glutathione
Up-Regulation
Down-Regulation

Keywords

  • Gastric ulcer
  • Indomethacin
  • Matrix metalloproteinase
  • Melatonin
  • Non-steroidal anti-inflammatory drug

ASJC Scopus subject areas

  • Endocrinology

Cite this

Effect of melatonin on secreted and induced matrix metalloproteinase-9 and -2 activity during prevention of indomethacin-induced gastric ulcer. / Ganguly, Krishnendu; Maity, Pallab; Reiter, Russel J; Swarnakar, Snehasikta.

In: Journal of Pineal Research, Vol. 39, No. 3, 10.2005, p. 307-315.

Research output: Contribution to journalArticle

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