Relationship of endothelin-1 and NLRP3 inflammasome activation in HT22 hippocampal cells in diabetes

Rebecca Ward, Adviye Ergul

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Diabetes increases the risk and worsens the progression of cognitive decline. Diabetic rats treated with the dual endothelin receptor antagonist bosentan, have been shown to improve hippocampal-based cognitive deficits. The NLRP3 inflammasome has been implicated in vascular complications of diabetes. We hypothesized that diabetes-mediated increase in endothelin-1 (ET-1) in hippocampal cells causes NLRP3 activation and inflammation. An in vitro model was employed by exposing HT22 hippocampal cells to normal (25 mM), low (5.5 mM) and high (50 mM) glucose conditions with and without palmitate (200 μM) in the presence and absence of 10 μM bosentan for 24 h. NLRP3 activity was measured by western blotting for cryopyrin and caspase-1. ET-1 and IL-1β expression was determined by ELISA. HT22 cells synthesize high levels of ET-1 in normal conditions, which was reduced with palmitate and bosentan as well as low and high glucose conditions. Decreased ET-1 levels were associated with greater activation of NLRP3 and IL-1β in normal glucose. High glucose increased NLRP3 markers and activation compared to normal and low glucose. These data suggest that ET-1 may be protective to neurons. Although endothelin antagonism may be beneficial in improving vascular dysfunction and cognitive impairment, its impact on hippocampal neurons should be further explored.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalLife sciences
Volume159
DOIs
StatePublished - Aug 15 2016

Fingerprint

Inflammasomes
Endothelin-1
Medical problems
Chemical activation
Glucose
Palmitates
Interleukin-1
Neurons
Blood Vessels
Caspase 1
Endothelins
Diabetes Complications
Rats
Western Blotting
Enzyme-Linked Immunosorbent Assay
Inflammation
bosentan

Keywords

  • Diabetes
  • Endothelin
  • Hippocampus
  • NLRP3 inflammasome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Relationship of endothelin-1 and NLRP3 inflammasome activation in HT22 hippocampal cells in diabetes. / Ward, Rebecca; Ergul, Adviye.

In: Life sciences, Vol. 159, 15.08.2016, p. 97-103.

Research output: Contribution to journalArticle

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