PMID- 29947543
OWN - NLM
STAT- MEDLINE
DCOM- 20181015
LR  - 20190906
IS  - 1802-9973 (Electronic)
IS  - 0862-8408 (Linking)
VI  - 67
IP  - Suppl 1
DP  - 2018 Jun 27
TI  - Endothelin-1 inhibition improves the mBDNF/proBDNF ratio in endothelial cells and 
      HT22 neurons under high glucose/palmitate growth conditions.
PG  - S237-S246
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 ET(B) 
      receptor selective antagonist BQ788 (1 microM) or dual-receptor antagonist 
      bosentan (10 microM). 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.
FAU - Ward, R
AU  - Ward R
AD  - Department of Neuroscience and Regenerative Medicine and Department of 
      Physiology, Augusta University, Augusta, GA, USA. aergul@augusta.edu.
FAU - Abdul, Y
AU  - Abdul Y
FAU - Ergul, A
AU  - Ergul A
LA  - eng
PT  - Journal Article
PL  - Czech Republic
TA  - Physiol Res
JT  - Physiological research
JID - 9112413
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Endothelin-1)
RN  - 0 (Palmitates)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Line, Transformed
MH  - Endothelial Cells/drug effects/*metabolism
MH  - Endothelin-1/antagonists & inhibitors/*metabolism
MH  - Glucose/*toxicity
MH  - Hippocampus/cytology/drug effects/metabolism
MH  - Mice
MH  - Neurons/drug effects/*metabolism
MH  - Palmitates/*toxicity
EDAT- 2018/06/28 06:00
MHDA- 2018/10/16 06:00
CRDT- 2018/06/28 06:00
PHST- 2018/06/28 06:00 [entrez]
PHST- 2018/06/28 06:00 [pubmed]
PHST- 2018/10/16 06:00 [medline]
AID - 933837 [pii]
AID - 10.33549/physiolres.933837 [doi]
PST - ppublish
SO  - Physiol Res. 2018 Jun 27;67(Suppl 1):S237-S246. doi: 10.33549/physiolres.933837.