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RETRACTED ARTICLE

Chronic gastric ulceration causes matrix metalloproteinases-9 and -3 augmentation: alleviation by melatonin.
Biochimie. 2012 Dec; 94(12):2687-98.B

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable of degradation of extracellular matrix (ECM) and key player in various inflammatory diseases. We investigated the regulation of MMPs in chronic gastric ulceration in mice. We generated chronic gastric ulcers in mice by indomethacin and examined the activity and expression of MMP-9 and -3 in stomach. Melatonin (N-acetyl-5-methoxytryptamine) treatment has also been applied to mice to characterize the changes in expression and activities of MMPs in gastric tissues. We observed significant upregulation of MMP-9 and -3 expressions and activities in stomach with increasing doses and duration of indomethacin that corroborated with increased activity of activator protein (AP)-1. Substantial damage in gastric epithelial layer was found during chronic ulceration. Melatonin suppressed MMP-9 and -3 expressions and activities during prevention and healing of chronic gastric ulcers. It also suppressed protein oxidation, lipid peroxidation and antioxidant enzymes. Additionally, expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-8 was significantly high in ulcerated stomachs while melatonin treatment blocked them to control level. We found elevated phosphorylation of extracellular-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) during chronic gastric ulceration, which were significantly reversed by melatonin. Moreover, expression of NF-κB, c-fos and c-jun were inhibited by melatonin resulting down regulation of MMP-9 and -3 expressions. In summary, oxidative stress is preceded by chronic inflammation that enhances the expression of MMP-9 and -3, while melatonin arrests both of them via reduction of AP-1 activity during protection of ulcer.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Ganguly K
Department of Physiology, Drug Development Diagnostics and Biotechnology Division, CSIR-Indian Institute of Chemical Biology, 4, Raja SC Mullick Road, Jadavpur, Kolkata 700032, India.
Swarnakar S
No affiliation info available

MeSH

AnimalsAntioxidantsBlotting, WesternChronic DiseaseExtracellular Signal-Regulated MAP KinasesGastric MucosaIndomethacinInterleukin-1betaInterleukin-8JNK Mitogen-Activated Protein KinasesLipid PeroxidationMatrix Metalloproteinase 3Matrix Metalloproteinase 9MelatoninMiceMice, Inbred BALB CNF-kappa BProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junReverse Transcriptase Polymerase Chain ReactionStomachStomach UlcerTranscription Factor AP-1Tumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Retracted Publication

Language

eng

PubMed ID

22959068

Citation

Ganguly, Krishnendu, and Snehasikta Swarnakar. "Chronic Gastric Ulceration Causes Matrix Metalloproteinases-9 and -3 Augmentation: Alleviation By Melatonin." Biochimie, vol. 94, no. 12, 2012, pp. 2687-98.
Ganguly K, Swarnakar S. Chronic gastric ulceration causes matrix metalloproteinases-9 and -3 augmentation: alleviation by melatonin. Biochimie. 2012;94(12):2687-98.
Ganguly, K., & Swarnakar, S. (2012). Chronic gastric ulceration causes matrix metalloproteinases-9 and -3 augmentation: alleviation by melatonin. Biochimie, 94(12), 2687-98. https://doi.org/10.1016/j.biochi.2012.08.004
Ganguly K, Swarnakar S. Chronic Gastric Ulceration Causes Matrix Metalloproteinases-9 and -3 Augmentation: Alleviation By Melatonin. Biochimie. 2012;94(12):2687-98. PubMed PMID: 22959068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic gastric ulceration causes matrix metalloproteinases-9 and -3 augmentation: alleviation by melatonin. AU - Ganguly,Krishnendu, AU - Swarnakar,Snehasikta, Y1 - 2012/08/13/ PY - 2012/03/16/received PY - 2012/08/07/accepted PY - 2012/9/11/entrez PY - 2012/9/11/pubmed PY - 2013/3/6/medline SP - 2687 EP - 98 JF - Biochimie JO - Biochimie VL - 94 IS - 12 N2 - Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable of degradation of extracellular matrix (ECM) and key player in various inflammatory diseases. We investigated the regulation of MMPs in chronic gastric ulceration in mice. We generated chronic gastric ulcers in mice by indomethacin and examined the activity and expression of MMP-9 and -3 in stomach. Melatonin (N-acetyl-5-methoxytryptamine) treatment has also been applied to mice to characterize the changes in expression and activities of MMPs in gastric tissues. We observed significant upregulation of MMP-9 and -3 expressions and activities in stomach with increasing doses and duration of indomethacin that corroborated with increased activity of activator protein (AP)-1. Substantial damage in gastric epithelial layer was found during chronic ulceration. Melatonin suppressed MMP-9 and -3 expressions and activities during prevention and healing of chronic gastric ulcers. It also suppressed protein oxidation, lipid peroxidation and antioxidant enzymes. Additionally, expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-8 was significantly high in ulcerated stomachs while melatonin treatment blocked them to control level. We found elevated phosphorylation of extracellular-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) during chronic gastric ulceration, which were significantly reversed by melatonin. Moreover, expression of NF-κB, c-fos and c-jun were inhibited by melatonin resulting down regulation of MMP-9 and -3 expressions. In summary, oxidative stress is preceded by chronic inflammation that enhances the expression of MMP-9 and -3, while melatonin arrests both of them via reduction of AP-1 activity during protection of ulcer. SN - 1638-6183 UR - https://www.unboundmedicine.com/medline/citation/22959068/Chronic_gastric_ulceration_causes_matrix_metalloproteinases_9_and__3_augmentation:_alleviation_by_melatonin_ DB - PRIME DP - Unbound Medicine ER -