Endothelin-1 inhibition improves the mBDNF/proBDNF ratio in endothelial cells and HT22 neurons under high glucose/palmitate growth conditions

R. Ward, Y. Abdul, Adviye Ergul

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Diabetes increases the risk and worsens the progression of cognitive impairment. The hippocampus is an important domain for learning and memory. We previously showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and endothelial cells within the neurovascular unit depend on each other for proper function, we investigated the effect of ET-1 on brain-derived neurotrophic factor (BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22 hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under normal and diabetes-mimicking (high glucose plus palmitate) conditions. Cells were treated with exogenous ET-1 or ET receptor antagonists including ETB receptor selective antagonist BQ788 (1 μM) or dual-receptor antagonist bosentan (10 μM). Mature (m)BDNF, proBDNF and caspase-3 levels were measured by Western blotting. Diabetic conditions reduced the prosurvival mBDNF/proBDNF ratio in both HT22 and BMEC-5i cells. Addition of exogenous ET-1 had no effect on the BDNF system in HT22 cells in diabetic conditions. Both HT22 and BMEC-5i cells had an increase in the mBDNF/proBDNF ratio when grown in diabetes-simulating conditions in the presence of endothelin receptor inhibition. These data suggest that blockade of ET-1 may provide neuroprotection to hippocampal cells through the modulation of the BDNF system.

Original languageEnglish (US)
Pages (from-to)S237-S246
JournalPhysiological Research
Volume67
StatePublished - Jan 1 2018

Fingerprint

Palmitates
Endothelin-1
Endothelial Cells
Brain-Derived Neurotrophic Factor
Neurons
Glucose
Growth
Endothelin Receptors
Nerve Growth Factors
Neuroprotective Agents
Caspase 3
Inhibition (Psychology)
Hippocampus
Western Blotting
Learning
Inflammation
Brain

Keywords

  • Diabetes
  • Endothelin
  • Mature BDNF
  • ProBDNF

ASJC Scopus subject areas

  • Physiology

Cite this

Endothelin-1 inhibition improves the mBDNF/proBDNF ratio in endothelial cells and HT22 neurons under high glucose/palmitate growth conditions. / Ward, R.; Abdul, Y.; Ergul, Adviye.

In: Physiological Research, Vol. 67, 01.01.2018, p. S237-S246.

Research output: Contribution to journalArticle

@article{63d768daf3d245059d11861fb23828a3,
title = "Endothelin-1 inhibition improves the mBDNF/proBDNF ratio in endothelial cells and HT22 neurons under high glucose/palmitate growth conditions",
abstract = "Diabetes increases the risk and worsens the progression of cognitive impairment. The hippocampus is an important domain for learning and memory. We previously showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and endothelial cells within the neurovascular unit depend on each other for proper function, we investigated the effect of ET-1 on brain-derived neurotrophic factor (BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22 hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under normal and diabetes-mimicking (high glucose plus palmitate) conditions. Cells were treated with exogenous ET-1 or ET receptor antagonists including ETB receptor selective antagonist BQ788 (1 μM) or dual-receptor antagonist bosentan (10 μM). Mature (m)BDNF, proBDNF and caspase-3 levels were measured by Western blotting. Diabetic conditions reduced the prosurvival mBDNF/proBDNF ratio in both HT22 and BMEC-5i cells. Addition of exogenous ET-1 had no effect on the BDNF system in HT22 cells in diabetic conditions. Both HT22 and BMEC-5i cells had an increase in the mBDNF/proBDNF ratio when grown in diabetes-simulating conditions in the presence of endothelin receptor inhibition. These data suggest that blockade of ET-1 may provide neuroprotection to hippocampal cells through the modulation of the BDNF system.",
keywords = "Diabetes, Endothelin, Mature BDNF, ProBDNF",
author = "R. Ward and Y. Abdul and Adviye Ergul",
year = "2018",
month = "1",
day = "1",
language = "English (US)",
volume = "67",
pages = "S237--S246",
journal = "Physiological Research",
issn = "0862-8408",
publisher = "Czech Academy of Sciences",

}

TY - JOUR

T1 - Endothelin-1 inhibition improves the mBDNF/proBDNF ratio in endothelial cells and HT22 neurons under high glucose/palmitate growth conditions

AU - Ward, R.

AU - Abdul, Y.

AU - Ergul, Adviye

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Diabetes increases the risk and worsens the progression of cognitive impairment. The hippocampus is an important domain for learning and memory. We previously showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and endothelial cells within the neurovascular unit depend on each other for proper function, we investigated the effect of ET-1 on brain-derived neurotrophic factor (BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22 hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under normal and diabetes-mimicking (high glucose plus palmitate) conditions. Cells were treated with exogenous ET-1 or ET receptor antagonists including ETB receptor selective antagonist BQ788 (1 μM) or dual-receptor antagonist bosentan (10 μM). Mature (m)BDNF, proBDNF and caspase-3 levels were measured by Western blotting. Diabetic conditions reduced the prosurvival mBDNF/proBDNF ratio in both HT22 and BMEC-5i cells. Addition of exogenous ET-1 had no effect on the BDNF system in HT22 cells in diabetic conditions. Both HT22 and BMEC-5i cells had an increase in the mBDNF/proBDNF ratio when grown in diabetes-simulating conditions in the presence of endothelin receptor inhibition. These data suggest that blockade of ET-1 may provide neuroprotection to hippocampal cells through the modulation of the BDNF system.

AB - Diabetes increases the risk and worsens the progression of cognitive impairment. The hippocampus is an important domain for learning and memory. We previously showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and endothelial cells within the neurovascular unit depend on each other for proper function, we investigated the effect of ET-1 on brain-derived neurotrophic factor (BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22 hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under normal and diabetes-mimicking (high glucose plus palmitate) conditions. Cells were treated with exogenous ET-1 or ET receptor antagonists including ETB receptor selective antagonist BQ788 (1 μM) or dual-receptor antagonist bosentan (10 μM). Mature (m)BDNF, proBDNF and caspase-3 levels were measured by Western blotting. Diabetic conditions reduced the prosurvival mBDNF/proBDNF ratio in both HT22 and BMEC-5i cells. Addition of exogenous ET-1 had no effect on the BDNF system in HT22 cells in diabetic conditions. Both HT22 and BMEC-5i cells had an increase in the mBDNF/proBDNF ratio when grown in diabetes-simulating conditions in the presence of endothelin receptor inhibition. These data suggest that blockade of ET-1 may provide neuroprotection to hippocampal cells through the modulation of the BDNF system.

KW - Diabetes

KW - Endothelin

KW - Mature BDNF

KW - ProBDNF

UR - http://www.scopus.com/inward/record.url?scp=85049175988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049175988&partnerID=8YFLogxK

M3 - Article

VL - 67

SP - S237-S246

JO - Physiological Research

JF - Physiological Research

SN - 0862-8408

ER -