Suppression of endothelin-converting enzyme-1 during buccal mucosal ulcer healing: effect of chronic alcohol ingestion.
Among the factors affecting the efficiency of soft oral tissue healing is endothelin-1 (ET-1), a potent vasoactive peptide produced from a biologically inactive big ET-1 by the action of endothelin-converting enzyme-1 (ECE-1). We investigated the expression of ECE-1 during buccal mucosal ulcer healing in rats maintained for 5 weeks on alcohol containing or control diet. The mucosal activity of ECE-1, characterized by sensitivity to phosphoramidon, was associated with microsomal fraction and showed an elevated (3.1-fold) level in the alcohol diet group. Moreover, the ulcer onset in the alcohol group was reflected in a 39% greater expression of ECE-1 activity, and was accompanied by a 1.4-fold greater increase in TNF-alpha and a 2.5-fold greater enhancement in epithelial cell apoptosis. While in both groups the ulcer healing was associated with a decrease in buccal mucosal expression of ECE-1, as well as a decline in TNF-alpha and apoptosis, the changes were significantly slower in the alcohol diet group and manifested by a 40% delay in healing. Thus, chronic alcohol ingestion leads to up-regulation of ECE-1 expression, induction of TNF-alpha, and triggering apoptotic events that delay the mucosal repair.
Slomiany
B L
BL
Research Center, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, 07103-2400, USA. slomiabr@umdnj.edu
Piotrowski
J
J
Slomiany
A
A
D000818:Animals; D017209:Apoptosis; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D000072396:Endothelin-Converting Enzymes; D004847:Epithelial Cells / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects*; D007976:Leupeptins / Q000494:pharmacology; D008666:Metalloendopeptidases; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D019226:Oral Ulcer / Q000378:metabolism*; D010436:Pepstatins / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014105:Tosyl Compounds / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014945:Wound Healing / Q000187:drug effects*
D007976:Leupeptins; D010436:Pepstatins; D011480:Protease Inhibitors; D014105:Tosyl Compounds; D014409:Tumor Necrosis Factor-alpha; C014195:Streptomyces pepsin inhibitor; D000431:Ethanol; C003614:4-toluenesulfonyl fluoride; D004492:Edetic Acid; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C032854:leupeptin; C031375:pepstatin