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Chuck Reynolds
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What does Resveratrol induce.? P-4

Published on 6/12/2019
For additional information  Click Here

Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition P-4

Results -Resveratrol induces autophagy through mTOR inhibition

In order to understand resveratrol-induced autophagy, we examined the effect of resveratrol on autophagy in GFP-LC3 expressing HeLa cells. Resveratrol treatment induces autophagy, as evidenced by the accumulation of LC3B-II and LC3 puncta formation Along with this result, treatment with mTOR kinase inhibitor pp242 demonstrated that mTORC1 activity is inversely correlated with the level of autophagy . This result implicates the possible involvement of mTORC1 in resveratrol-induced autophagy. To test the position of mTOR in resveratrol-induced autophagy, we used various drugs that induce autophagy.

We found that combinatory treatment with resveratrol and PP242 did not show any additive effect , indicating that resveratrol acts via the same pathway as PP242. Decreased cyclic-AMP (cAMP) levels induce autophagy in an mTOR-independent manner17. Because reduction of cAMP induces autophagy through inhibition of PKA, we utilized H-89, a PKA inhibitor, to induce mTOR-independent autophagy. As expected, treatment with H-89 increased autophagy without reduction of mTORC1 activity. Additionally, unlike the resveratrol-PP242 combination, co-treatment with H-89 and resveratrol or H-89 and PP242 had an additive effect on the accumulation of LC3B-II  This result indicates that H-89 induces autophagy through an mTOR-independent pathway, and resveratrol and H-89 use different pathways to induce autophagy. Taken together, these combinatory drug treatment experiments indicate that resveratrol induces autophagy at the level as same as mTOR inhibition.

Article Produced By
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea

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