TY - JOUR
T1 - Protection of the neurovascular unit from calcium-related ischemic injury by linalyl acetate
AU - Hsieh, Yu
AU - Shin, You
AU - Seol, Geun
N1 - Funding Information:
This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF-2018R1D1A1B07050048). This article is a
Publisher Copyright:
© 2021 Wolters Kluwer Medknow Publications. All rights reserved.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Calcium-related ischemic injury (CRII) can damage cells of the neurovascular unit (NVU). Here, we investigate the protective effects of linalyl acetate (LA) against CRII-induced NVU damage and evaluate the underlying mechanisms. The protective effects of LA in cell lines representative of NVU components (BEND, SH-SY5Y, BV2, and U373 cells) were evaluated following exposure to oxygen-glucose deprivation/reoxygenation alone (OGD/R-only) or OGD/R in the presence of 5 mM extracellular calcium ([Ca2+]o) to mimic CRII. LA reversed damage under OGD/R-only conditions by blocking p47phox/NADPH oxidase (NOX) 2 expression, reactive oxygen species (ROS) production, nitric oxide (NO) abnormality, and lactate dehydrogenase (LDH) release only in the BEND cells. However, under CRII-mimicking conditions, LA reversed NO abnormality and matrix metalloproteinase (MMP)-9 activation in the BEND murine brain endothelial cells; inhibited p47phoxexpression in the human SH-SY5Y neural-like cells; decreased NOX2 expression and ROS generation in the BV2 murine microglial cells; and reduced p47phoxexpression in the U373 human astrocyte-like cells. Importantly, LA protected against impairment of the neural cells, astrocytes, and microglia, all of which are cellular components of the NVU induced by exposure to CRII-mimicking conditions, by reducing LDH release.
AB - Calcium-related ischemic injury (CRII) can damage cells of the neurovascular unit (NVU). Here, we investigate the protective effects of linalyl acetate (LA) against CRII-induced NVU damage and evaluate the underlying mechanisms. The protective effects of LA in cell lines representative of NVU components (BEND, SH-SY5Y, BV2, and U373 cells) were evaluated following exposure to oxygen-glucose deprivation/reoxygenation alone (OGD/R-only) or OGD/R in the presence of 5 mM extracellular calcium ([Ca2+]o) to mimic CRII. LA reversed damage under OGD/R-only conditions by blocking p47phox/NADPH oxidase (NOX) 2 expression, reactive oxygen species (ROS) production, nitric oxide (NO) abnormality, and lactate dehydrogenase (LDH) release only in the BEND cells. However, under CRII-mimicking conditions, LA reversed NO abnormality and matrix metalloproteinase (MMP)-9 activation in the BEND murine brain endothelial cells; inhibited p47phoxexpression in the human SH-SY5Y neural-like cells; decreased NOX2 expression and ROS generation in the BV2 murine microglial cells; and reduced p47phoxexpression in the U373 human astrocyte-like cells. Importantly, LA protected against impairment of the neural cells, astrocytes, and microglia, all of which are cellular components of the NVU induced by exposure to CRII-mimicking conditions, by reducing LDH release.
KW - Calcium-related ischemic injury
KW - linalyl acetate
KW - neurovascular unit
UR - http://www.scopus.com/inward/record.url?scp=85105475310&partnerID=8YFLogxK
U2 - 10.4103/cjp.cjp_94_20
DO - 10.4103/cjp.cjp_94_20
M3 - Article
C2 - 33938819
AN - SCOPUS:85105475310
SN - 0304-4920
VL - 64
SP - 88
EP - 96
JO - Chinese Journal of Physiology
JF - Chinese Journal of Physiology
IS - 2
ER -