Cited by 39Nitric Oxide and Endothelin EffectsAlzheimer's disease research and treatmentsBarrier Structure and Function Studies

Endothelin-1 is Elevated in Alzheimer's Disease Brain Microvessels and is Neuroprotective

Luo, Jinhua, Grammas, Paula·2010·Journal of Alzheimer's Disease

Abstract

The vasoactive protein endothelin-1 (ET-1) is produced by vascular endothelial cells and participates in the regulation of vascular inflammation. We have previously documented that the cerebral microvasculature is a source of inflammatory proteins and a likely contributor to the pathogenesis of Alzheimer's disease (AD). In this study, we (a) compare expression of ET-1 in brain microvessels isolated from AD and control brains; (b) determine thrombin regulation of ET-1 synthesis and release in brain endothelial cells; and (c) assess the effects of ET-1 on neuronal viability in vitro. Western blot analysis indicates a significantly higher level of ET-1 in AD vessels compared to vessels from age-matched controls. ET-1 expression and secretion are both induced by the inflammatory and neurotoxic protein thrombin. Pretreatment of neuronal cultures with ET-1 significantly increases neuronal survival when cells are challenged with oxidative stress (H2O2) or thrombin. The protective effect of ET-1 is blocked by incubation with an inhibitor of the c-Jun kinase (JNK) cascade. These data demonstrate that in the brain microvasculature dysfunctional or stressed endothelial cells express ET-1 and that this protein promotes the survival of brain neurons exposed to injury.

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Crossref · 10.3233/jad-2010-091486

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Authors
Luo, J., & Grammas, P.
Affiliations
Texas Tech University (US)
Corresponding author
Grammas, Paula
Venue
Journal of Alzheimer's Disease
Published
2010-09-02
Volume
21
Issue
3
Pages
887-896
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
OpenAlex
W1590517687
Cited by
39
References
53
Citations by year
2024: 1 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 3 · 2012: 3
FWCI
2.60
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (AG 15964, AG-020569, AG028367, R01AG028367, R01AG020569, R01AG015964)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
endothelin-1, Alzheimer's disease
MeSH terms
Alzheimer Disease, Analysis of Variance, Animals, Brain, Cells, Cultured, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Humans, Neurons, Thrombin, Blotting, Western, Oxidative Stress, Endothelin-1, Reverse Transcriptase Polymerase Chain Reaction, Endothelial Cells, Rats, Microvessels

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