Palmitic acid-induced lipotoxicity and protection by (+)-catechin in rat cortical astrocytes

Kar Lok Wong, Yu Ru Wu, Ka Shun Cheng, Paul Chan, Chi Wai Cheung, Dah Yuu Lu, Tzu Hui Su, Zhong Min Liu, Yuk Man Leung

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background Astrocytes do not only maintain homeostasis of the extracellular milieu of the neurons, but also play an active role in modulating synaptic transmission. Palmitic acid (PA) is a saturated fatty acid which, when being excessive, is a significant risk factor for lipotoxicity. Activation of astrocytes by PA has been shown to cause neuronal inflammation and demyelination. However, direct damage by PA to astrocytes is relatively unexplored. The aim of this study was to identify the mechanism(s) of PA-induced cytotoxicity in rat cortical astrocytes and possible protection by (+)-catechin. Methods Cytotoxicity and endoplasmic reticulum (ER) markers were assessed by MTT assay and Western blotting, respectively. Cytosolic Ca 2+ and mitochondrial membrane potential (MMP) were measured microfluorimetrically using fura-2 and rhodamine 123, respectively. Intracellular reactive oxygen species (ROS) production was assayed by the indicator 2′-7′-dichlorodihydrofluorescein diacetate. Results Exposure of astrocytes to 100 μM PA for 24 h resulted in apoptotic cell death. Whilst PA-induced cell death appeared to be unrelated to ER stress and perturbation in cytosolic Ca2+ signaling, it was likely a result of ROS production and subsequent MMP collapse, since ascorbic acid (anti-oxidant, 100 μM) prevented PA-induced MMP collapse and cell death. Co-treatment of astrocytes with (+)-catechin (300 μM), an anti-oxidant found abundantly in green tea, significantly prevented PA-induced ROS production, MMP collapse and cell death. Conclusion Our results suggest that PA-induced cytotoxicity in astrocytes may involve ROS generation and MMP collapse, which can be prevented by (+)-catechin.

Original languageEnglish
Pages (from-to)1106-1113
Number of pages8
JournalPharmacological Reports
Volume66
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Palmitic Acid
Catechin
Astrocytes
Mitochondrial Membrane Potential
Reactive Oxygen Species
Cell Death
Oxidants
Rhodamine 123
Endoplasmic Reticulum Stress
Fura-2
Demyelinating Diseases
Tea
Synaptic Transmission
Endoplasmic Reticulum
Ascorbic Acid
Homeostasis
Fatty Acids
Western Blotting
Inflammation
Neurons

Keywords

  • Astrocytes
  • Mitochondrial membrane potential
  • Palmitic acid
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pharmacology

Cite this

Palmitic acid-induced lipotoxicity and protection by (+)-catechin in rat cortical astrocytes. / Wong, Kar Lok; Wu, Yu Ru; Cheng, Ka Shun; Chan, Paul; Cheung, Chi Wai; Lu, Dah Yuu; Su, Tzu Hui; Liu, Zhong Min; Leung, Yuk Man.

In: Pharmacological Reports, Vol. 66, No. 6, 2014, p. 1106-1113.

Research output: Contribution to journalArticle

Wong, KL, Wu, YR, Cheng, KS, Chan, P, Cheung, CW, Lu, DY, Su, TH, Liu, ZM & Leung, YM 2014, 'Palmitic acid-induced lipotoxicity and protection by (+)-catechin in rat cortical astrocytes', Pharmacological Reports, vol. 66, no. 6, pp. 1106-1113. https://doi.org/10.1016/j.pharep.2014.07.009
Wong, Kar Lok ; Wu, Yu Ru ; Cheng, Ka Shun ; Chan, Paul ; Cheung, Chi Wai ; Lu, Dah Yuu ; Su, Tzu Hui ; Liu, Zhong Min ; Leung, Yuk Man. / Palmitic acid-induced lipotoxicity and protection by (+)-catechin in rat cortical astrocytes. In: Pharmacological Reports. 2014 ; Vol. 66, No. 6. pp. 1106-1113.
@article{28caae52306049b298bce714dbbf4115,
title = "Palmitic acid-induced lipotoxicity and protection by (+)-catechin in rat cortical astrocytes",
abstract = "Background Astrocytes do not only maintain homeostasis of the extracellular milieu of the neurons, but also play an active role in modulating synaptic transmission. Palmitic acid (PA) is a saturated fatty acid which, when being excessive, is a significant risk factor for lipotoxicity. Activation of astrocytes by PA has been shown to cause neuronal inflammation and demyelination. However, direct damage by PA to astrocytes is relatively unexplored. The aim of this study was to identify the mechanism(s) of PA-induced cytotoxicity in rat cortical astrocytes and possible protection by (+)-catechin. Methods Cytotoxicity and endoplasmic reticulum (ER) markers were assessed by MTT assay and Western blotting, respectively. Cytosolic Ca 2+ and mitochondrial membrane potential (MMP) were measured microfluorimetrically using fura-2 and rhodamine 123, respectively. Intracellular reactive oxygen species (ROS) production was assayed by the indicator 2′-7′-dichlorodihydrofluorescein diacetate. Results Exposure of astrocytes to 100 μM PA for 24 h resulted in apoptotic cell death. Whilst PA-induced cell death appeared to be unrelated to ER stress and perturbation in cytosolic Ca2+ signaling, it was likely a result of ROS production and subsequent MMP collapse, since ascorbic acid (anti-oxidant, 100 μM) prevented PA-induced MMP collapse and cell death. Co-treatment of astrocytes with (+)-catechin (300 μM), an anti-oxidant found abundantly in green tea, significantly prevented PA-induced ROS production, MMP collapse and cell death. Conclusion Our results suggest that PA-induced cytotoxicity in astrocytes may involve ROS generation and MMP collapse, which can be prevented by (+)-catechin.",
keywords = "Astrocytes, Mitochondrial membrane potential, Palmitic acid, Reactive oxygen species",
author = "Wong, {Kar Lok} and Wu, {Yu Ru} and Cheng, {Ka Shun} and Paul Chan and Cheung, {Chi Wai} and Lu, {Dah Yuu} and Su, {Tzu Hui} and Liu, {Zhong Min} and Leung, {Yuk Man}",
year = "2014",
doi = "10.1016/j.pharep.2014.07.009",
language = "English",
volume = "66",
pages = "1106--1113",
journal = "Pharmacological Reports",
issn = "1734-1140",
publisher = "Polish Academy of Sciences Publishing House",
number = "6",

}

TY - JOUR

T1 - Palmitic acid-induced lipotoxicity and protection by (+)-catechin in rat cortical astrocytes

AU - Wong, Kar Lok

AU - Wu, Yu Ru

AU - Cheng, Ka Shun

AU - Chan, Paul

AU - Cheung, Chi Wai

AU - Lu, Dah Yuu

AU - Su, Tzu Hui

AU - Liu, Zhong Min

AU - Leung, Yuk Man

PY - 2014

Y1 - 2014

N2 - Background Astrocytes do not only maintain homeostasis of the extracellular milieu of the neurons, but also play an active role in modulating synaptic transmission. Palmitic acid (PA) is a saturated fatty acid which, when being excessive, is a significant risk factor for lipotoxicity. Activation of astrocytes by PA has been shown to cause neuronal inflammation and demyelination. However, direct damage by PA to astrocytes is relatively unexplored. The aim of this study was to identify the mechanism(s) of PA-induced cytotoxicity in rat cortical astrocytes and possible protection by (+)-catechin. Methods Cytotoxicity and endoplasmic reticulum (ER) markers were assessed by MTT assay and Western blotting, respectively. Cytosolic Ca 2+ and mitochondrial membrane potential (MMP) were measured microfluorimetrically using fura-2 and rhodamine 123, respectively. Intracellular reactive oxygen species (ROS) production was assayed by the indicator 2′-7′-dichlorodihydrofluorescein diacetate. Results Exposure of astrocytes to 100 μM PA for 24 h resulted in apoptotic cell death. Whilst PA-induced cell death appeared to be unrelated to ER stress and perturbation in cytosolic Ca2+ signaling, it was likely a result of ROS production and subsequent MMP collapse, since ascorbic acid (anti-oxidant, 100 μM) prevented PA-induced MMP collapse and cell death. Co-treatment of astrocytes with (+)-catechin (300 μM), an anti-oxidant found abundantly in green tea, significantly prevented PA-induced ROS production, MMP collapse and cell death. Conclusion Our results suggest that PA-induced cytotoxicity in astrocytes may involve ROS generation and MMP collapse, which can be prevented by (+)-catechin.

AB - Background Astrocytes do not only maintain homeostasis of the extracellular milieu of the neurons, but also play an active role in modulating synaptic transmission. Palmitic acid (PA) is a saturated fatty acid which, when being excessive, is a significant risk factor for lipotoxicity. Activation of astrocytes by PA has been shown to cause neuronal inflammation and demyelination. However, direct damage by PA to astrocytes is relatively unexplored. The aim of this study was to identify the mechanism(s) of PA-induced cytotoxicity in rat cortical astrocytes and possible protection by (+)-catechin. Methods Cytotoxicity and endoplasmic reticulum (ER) markers were assessed by MTT assay and Western blotting, respectively. Cytosolic Ca 2+ and mitochondrial membrane potential (MMP) were measured microfluorimetrically using fura-2 and rhodamine 123, respectively. Intracellular reactive oxygen species (ROS) production was assayed by the indicator 2′-7′-dichlorodihydrofluorescein diacetate. Results Exposure of astrocytes to 100 μM PA for 24 h resulted in apoptotic cell death. Whilst PA-induced cell death appeared to be unrelated to ER stress and perturbation in cytosolic Ca2+ signaling, it was likely a result of ROS production and subsequent MMP collapse, since ascorbic acid (anti-oxidant, 100 μM) prevented PA-induced MMP collapse and cell death. Co-treatment of astrocytes with (+)-catechin (300 μM), an anti-oxidant found abundantly in green tea, significantly prevented PA-induced ROS production, MMP collapse and cell death. Conclusion Our results suggest that PA-induced cytotoxicity in astrocytes may involve ROS generation and MMP collapse, which can be prevented by (+)-catechin.

KW - Astrocytes

KW - Mitochondrial membrane potential

KW - Palmitic acid

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=84908672634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908672634&partnerID=8YFLogxK

U2 - 10.1016/j.pharep.2014.07.009

DO - 10.1016/j.pharep.2014.07.009

M3 - Article

C2 - 25443742

AN - SCOPUS:84908672634

VL - 66

SP - 1106

EP - 1113

JO - Pharmacological Reports

JF - Pharmacological Reports

SN - 1734-1140

IS - 6

ER -