Gastric mucosal protection via enhancement of MUC5AC and MUC6 by geranylgeranylacetone.
The mucus layer that covers gastric mucosa is a powerful barrier that protects tissues from the hazardous gastric environment; however, the role of each gastric MUC type, such as MUC1, MUC5AC, and MUC6, has not been evaluated. The purpose of this study is to identify the MUC type, which plays a predominant role in this protective process by use of geranylgeranylacetone (GGA), a promising cytoprotective agent. In addition, the mechanism of mucus secretion promoted by GGA was investigated. Rat gastric mucosal damage was provoked using ethanol, and GGA was pretreated 1 hour before ethanol. GGA was found to significantly protect rats from ethanol-induced gastric damage by increasing mucus levels, MUC5AC and MUC6, especially at ethanol-induced ulcer margins, but not by MUC1. When expression of heat shock protein 70 (HSP70) and neuronal nitric oxide synthase (nNOS) was evaluated by Western blotting, both were found to be increased in GGA-treated ethanol rats. In addition, the cytoprotective effect of GGA was blocked by L-NMMA, a nonspecific NOS inhibitor, but not blocked by aminoguanidine, a specific inducible nitric oxide synthase inhibitor, thus indicating the participation of nNOS. In conclusion, GGA protected ethanol-induced gastric damage by upregulating MUC5AC and MUC6 rather than MUC1. In addition, HSP70 and nNOS were found to be involved in GGA cytoprotection, probably by increasing mucus production or secretion.
Nam
Su Youn
SY
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Chongno-Gu, Seoul, South Korea.
Kim
Nayoung
N
Lee
Chang Soo
CS
Choi
Kee Don
KD
Lee
Hye Seung
HS
Jung
Hyun Chae
HC
Song
In Sung
IS
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism; D008297:Male; D055271:Mucin 5AC; D018396:Mucin-1; D055272:Mucin-6; D009077:Mucins / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000473:pathology; D013272:Stomach Diseases / Q000139:chemically induced / Q000188:drug therapy
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D006595:Hexosamines; C506177:MUC1 protein, rat; C524680:Muc5ac protein, rat; C524736:Muc6 protein, rat; D055271:Mucin 5AC; D018396:Mucin-1; D055272:Mucin-6; D009077:Mucins; D000431:Ethanol; D052248:Nitric Oxide Synthase Type I; D051546:Cyclooxygenase 2; C031049:geranylgeranylacetone