SIRT1 activation alleviates brain microvascular endothelial dysfunction in peroxisomal disorders

Zhang,Yunshan; Cui,Guiyun; Wang,Yue; Gong,Yi; Wang,Yulan

doi:10.3892/ijmm.2019.4250

SIRT1 activation alleviates brain microvascular endothelial dysfunction in peroxisomal disorders

Authors:
- Yunshan Zhang
- Guiyun Cui
- Yue Wang
- Yi Gong
- Yulan Wang
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Affiliations: Department of Anatomy and Embryology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China, Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China, Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China
Published online on: June 20, 2019 https://doi.org/10.3892/ijmm.2019.4250
Pages: 995-1005
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Peroxisomal disorders are genetically heterogeneous metabolic disorders associated with a deficit of very long chain fatty acid β‑oxidation that commonly manifest as early‑onset neurodegeneration. Brain microvascular endothelial dysfunction with increased permeability to monocytes has been described in X‑linked adrenoleukodystrophy, one of the most common peroxisomal disorders caused by mutations of the ATP binding cassette subfamily D member 1 (ABCD1) gene. The present study demonstrated that dysregulation of sirtuin 1 (SIRT1) in human brain microvascular endothelial cells (HBMECs) mediates changes in adhesion molecules and tight‑junction protein expression, as well as increased adhesion to monocytes associated with peroxisomal dysfunction due to ABCD1 or hydroxysteroid 17‑β dehydrogenase 4 silencing. Furthermore, enhancement of the function of SIRT1 by resveratrol attenuated this molecular and functional dysregulation of HBMECs via modulation of the nuclear factor‑κB and Krüppel‑like factor 4 signaling pathways.

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