Ammonium glycyrrhizinate protects gastric epithelial cells from hydrogen peroxide-induced cell death.
Glycyrrhiza uralensis has a potential for preventing or ameliorating gastric mucosal ulceration. To understand the molecular mechanism about the medicinal effect of G. uralensis, we isolated four single compounds from G. uralensis and one related compound and screened for the cellular protective effect against H(2)O(2)-induced damage in gastric epithelial AGS cells. Interestingly, we found that ammonium glycyrrhizinate (AG) prepared from glycyrrhizin dramatically protects AGS cells from H(2)O(2)-induced damage as measured by the integrity of actin cytoskeleton. AG also inhibited FeSO(4)-induced reactive oxygen radicals in a dose-dependent manner, suggesting the role for AG as a free radical scavenger. To better understand the protective role of AG at the transcriptional level, we performed genome-wide expression profiling using high-density oligonucleotide microarrays, followed by validation using RT-PCR. Among the 33,096 genes that were screened in the microarray, 936 genes were found to be differentially expressed in a statistically significant manner in the presence or absence of H(2)O(2) and AG. Among the 936 genes, 51 genes were differentially expressed at least 3-fold in response to the H(2)O(2) treatment. AG blocked the expression of genes related to apoptotic cell death (GDF15, ATF3, TNFRSF10A, NALP1) or oxidative stress path-ways (HMOX1) which was elevated in response to H(2)O(2) treatment, suggesting a potential protective role for AG in oxidative stress-induced cell death. Collectively, current results demonstrate that AG is a novel antioxidant that could be effective for the treatment of gastric diseases related to the oxidative stress-induced mucosal damage.
Oh
Hyun-Mee
HM
Department of Life Sciences, GIST, Gwangju 500-712, Korea.
Lee
Sungga
S
Park
Young-Na
YN
Choi
Eun-Ju
EJ
Choi
Ji-Young
JY
Kim
Jeong Ah
JA
Kweon
Ji-Hye
JH
Han
Weon-Cheol
WC
Choi
Suck-Chei
SC
Han
Joung-Kyue
JK
Son
Jong-Keun
JK
Lee
Seung-Ho
SH
Jun
Chang-Duk
CD
D000199:Actins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D016000:Cluster Analysis; D019610:Cytoprotection / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry; D019695:Glycyrrhizic Acid / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D013270:Stomach / Q000166:cytology*
D000199:Actins; D019695:Glycyrrhizic Acid; D006861:Hydrogen Peroxide