Aged garlic extract enhances heme oxygenase-1 and glutamate-cysteine ligase modifier subunit expression via the nuclear factor erythroid 2-related factor 2-antioxidant response element signaling pathway in human endothelial cells.
The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway defends cells against oxidative stress and regulates the cellular redox balance. Activation of this pathway induces a variety of antioxidant enzymes, resulting in the protection of our bodies against oxidative damage. It has been reported that aged garlic extract (AGE), a garlic preparation that is rich in water-soluble cysteinyl moieties, reduces oxidative stress and helps to ameliorate of cardiovascular, renal and hepatic diseases. We hypothesized that AGE enhances the expression of antioxidant enzymes via the Nrf2-ARE pathway in human umbilical vein endothelial cells in culture. Gene expression of antioxidant enzymes was measured using real-time polymerase chain reaction. Nuclear accumulation of Nrf2 and antioxidant enzymes expression were evaluated using western blotting analyses. We found that AGE promoted the accumulation of Nrf2 into the nucleus in a time- and dose-dependent manner and increased the gene expression and polypeptide level of heme oxygenase-1 (HO-1) and glutamate-cysteine ligase modifier subunit (GCLM). Moreover, the effect of AGE in elevating the gene expression of HO-1 and GCLM was found to be mediated via Nrf2 activation in human umbilical vein endothelial cells. Taken together, these observations suggest that AGE induces the expression of HO-1 and GCLM, which are antioxidant enzymes, via activation of the Nrf2-ARE signaling pathway.
Central Research Institute, Wakunaga Pharmaceutical Co. Ltd., 1624 Shimokotachi, Kodacho, Akitakata, Hiroshima 739-1195, Japan.
Kei
K
Hiramatsu
Central Research Institute, Wakunaga Pharmaceutical Co. Ltd., 1624 Shimokotachi, Kodacho, Akitakata, Hiroshima 739-1195, Japan.
Tadamitsu
T
Tsuneyoshi
Central Research Institute, Wakunaga Pharmaceutical Co. Ltd., 1624 Shimokotachi, Kodacho, Akitakata, Hiroshima 739-1195, Japan.
Takahiro
T
Ogawa
Central Research Institute, Wakunaga Pharmaceutical Co. Ltd., 1624 Shimokotachi, Kodacho, Akitakata, Hiroshima 739-1195, Japan. Electronic address: morihara_n@wakunaga.co.jp.
Naoaki
N
Morihara
D021581:Active Transport, Cell Nucleus; D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D004790:Enzyme Induction; D005737:Garlic / Q000737:chemistry*; D005721:Glutamate-Cysteine Ligase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010936:Plant Extracts / Q000378:metabolism*; D018517:Plant Roots / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D034741:RNA, Small Interfering; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase
Aged garlic extract; Antioxidant; GCLM; HO-1; Nrf2-ARE signaling pathway