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Sulforaphane Inhibits MGO-AGE-Mediated Neuroinflammation by Suppressing NF-?B, MAPK, and AGE-RAGE Signaling Pathways in Microglial Cells.

ABSTRACT: Advanced glycation end products (AGEs) are produced through the binding of glycated protein or lipid with sugar, and they are known to be involved in the pathogenesis of both age-dependent and independent neurological complications. Among dicarbonyl compounds, methylglyoxal (MGO), which is produced from glucose breakdown, is a key precursor of AGE formation and neurotoxicity. Several studies have shown the toxic effects of bovine serum albumin (BSA)-AGE (prepared with glucose, sucrose or fructose) both in in vitro and in vivo. In fact, MGO-derived AGEs (MGO-AGEs) are highly toxic to neurons and other cells of the central nervous system. Therefore, we aimed to investigate the role of MGO-AGEs in microglial activation, a key inflammatory event, or secondary brain damage in neuroinflammatory diseases. Interestingly, we found that sulforaphane (SFN) as a potential candidate to downregulate neuroinflammation induced by MGO-AGEs in BV2 microglial cells. SFN not only inhibited the formation of MGO-AGEs, but it did not show breaking activity on the MGO-mediated AGEs cross-links with protein, indicating that SFN could potentially trap MGO or inhibit toxic AGE damage. In addition, SFN significantly attenuated the production of neuroinflammatory mediators induced by MGO-AGEs in BV2 microglial cells. SFN also lowered the expression levels of AGE receptor (RAGE) in microglial cells, suggesting that SFN could downregulate MGO-AGE-mediated neurotoxicity at the receptor activation level. Altogether, our current study revealed that SFN might show neuropharmacological potential for downregulating MGO-AGEs-mediated neuronal complications thorough attenuating AGE formation and neuroinflammatory responses induced by MGO-AGEs in vitro.

SUBMITTER: Subedi L

PROVIDER: S-EPMC7554773 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Sulforaphane Inhibits MGO-AGE-Mediated Neuroinflammation by Suppressing NF-κB, MAPK, and AGE-RAGE Signaling Pathways in Microglial Cells.

Subedi Lalita L Lee Jae Hyuk JH Gaire Bhakta Prasad BP Kim Sun Yeou SY

Antioxidants (Basel, Switzerland) 20200826 9

Advanced glycation end products (AGEs) are produced through the binding of glycated protein or lipid with sugar, and they are known to be involved in the pathogenesis of both age-dependent and independent neurological complications. Among dicarbonyl compounds, methylglyoxal (MGO), which is produced from glucose breakdown, is a key precursor of AGE formation and neurotoxicity. Several studies have shown the toxic effects of bovine serum albumin (BSA)-AGE (prepared with glucose, sucrose or fructos ...[more]

PMID: 32859007

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Dataset Information

Sulforaphane Inhibits MGO-AGE-Mediated Neuroinflammation by Suppressing NF-?B, MAPK, and AGE-RAGE Signaling Pathways in Microglial Cells.

Publications

Sulforaphane Inhibits MGO-AGE-Mediated Neuroinflammation by Suppressing NF-κB, MAPK, and AGE-RAGE Signaling Pathways in Microglial Cells.

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