Cholesterol sulfate alters astrocyte metabolism and provides protection against oxidative stress

Jude Prah, Ali Winters, Kiran Chaudhari, Jessica Hersh, Ran Liu, Shao Hua Yang

Research output: Contribution to journalArticle

Abstract

Cholesterol sulfate (CS) is one of the most important known sterol sulfates in human plasma and it is present as a normal constituent in a variety of human tissues. In both the brain and periphery, CS serves as a substrate for the synthesis of sulfonated adrenal steroids such as pregnenolone sulfate and dehydroepiandrosterone (DHEA) sulfate and as a constituent of many biological membranes including red blood cells where it functions as a stabilizing agent. It also acts as an endogenous regulator of cholesterol synthesis. However, the role of CS in brain metabolism and neurological disorder is unclear. In the current study we investigated the neuroprotective action of CS as well as its role in brain energy metabolism. The neuroprotective effect of CS and its role on cell metabolism were determined in primary astrocyte prepared from the cortex of postnatal day 0–2 C57BL/6 pups and a hippocampal HT-22 cell line using Calcein AM and MTT cell viability assay, flow cytometry, Seahorse extracellular flux analysis, and metabolism assay kits. We found that CS attenuates glutamate and rotenone induced cell death in HT-22 cells, decrease glutamate induced mitochondria membrane potential collapse, and reactive oxygen species production. Additionally, CS activates the Akt/Bcl2 pathway. We observed that CS impacts astrocyte metabolism by increasing mitochondrial phosphorylation, ATP, and glycogen contents. Our study demonstrated that CS modulates brain energy metabolism and its neuroprotective effects might be due to the activation of Akt signaling or its ability to decrease reactive oxygen species production.

Original languageEnglish
Article number146378
JournalBrain Research
Volume1723
DOIs
StatePublished - 15 Nov 2019

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Astrocytes
Oxidative Stress
Neuroprotective Agents
Energy Metabolism
Glutamic Acid
Reactive Oxygen Species
Brain
Smegmamorpha
cholesteryl sulfate
Rotenone
Dehydroepiandrosterone Sulfate
Excipients
Brain Diseases
Sterols
Nervous System Diseases
Glycogen
Membrane Potentials
Sulfates
Cell Survival
Flow Cytometry

Keywords

  • Astrocytes
  • Cholesterol sulfate
  • Metabolism
  • Neuroprotection
  • Oxidative stress

Cite this

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abstract = "Cholesterol sulfate (CS) is one of the most important known sterol sulfates in human plasma and it is present as a normal constituent in a variety of human tissues. In both the brain and periphery, CS serves as a substrate for the synthesis of sulfonated adrenal steroids such as pregnenolone sulfate and dehydroepiandrosterone (DHEA) sulfate and as a constituent of many biological membranes including red blood cells where it functions as a stabilizing agent. It also acts as an endogenous regulator of cholesterol synthesis. However, the role of CS in brain metabolism and neurological disorder is unclear. In the current study we investigated the neuroprotective action of CS as well as its role in brain energy metabolism. The neuroprotective effect of CS and its role on cell metabolism were determined in primary astrocyte prepared from the cortex of postnatal day 0–2 C57BL/6 pups and a hippocampal HT-22 cell line using Calcein AM and MTT cell viability assay, flow cytometry, Seahorse extracellular flux analysis, and metabolism assay kits. We found that CS attenuates glutamate and rotenone induced cell death in HT-22 cells, decrease glutamate induced mitochondria membrane potential collapse, and reactive oxygen species production. Additionally, CS activates the Akt/Bcl2 pathway. We observed that CS impacts astrocyte metabolism by increasing mitochondrial phosphorylation, ATP, and glycogen contents. Our study demonstrated that CS modulates brain energy metabolism and its neuroprotective effects might be due to the activation of Akt signaling or its ability to decrease reactive oxygen species production.",
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Cholesterol sulfate alters astrocyte metabolism and provides protection against oxidative stress. / Prah, Jude; Winters, Ali; Chaudhari, Kiran; Hersh, Jessica; Liu, Ran; Yang, Shao Hua.

In: Brain Research, Vol. 1723, 146378, 15.11.2019.

Research output: Contribution to journalArticle

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AU - Liu, Ran

AU - Yang, Shao Hua

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