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Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.

Publication ,  Journal Article
Wang, S; Li, B; Solomon, V; Fonteh, A; Rapoport, SI; Bennett, DA; Arvanitakis, Z; Chui, HC; Sullivan, PM; Yassine, HN
Published in: Mol Neurodegener
June 15, 2022

BACKGROUND: Apolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer's disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A2 (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known. METHODS: Mouse primary astrocytes, mouse and human brain samples differing by APOE genotypes were collected for measuring cPLA2 expression, phosphorylation, and activity in relation to measures of inflammation and oxidative stress. RESULTS: Greater cPLA2 phosphorylation, cPLA2 activity and leukotriene B4 (LTB4) levels were identified in ApoE4 compared to ApoE3 in primary astrocytes, brains of ApoE-targeted replacement (ApoE-TR) mice, and in human brain homogenates from the inferior frontal cortex of persons with AD dementia carrying APOE3/4 compared to APOE3/3. Higher phosphorylated p38 MAPK but not ERK1/2 was found in ApoE4 primary astrocytes and mouse brains than that in ApoE3. Greater cPLA2 translocation to cytosol was observed in human postmortem frontal cortical synaptosomes with recombinant ApoE4 than ApoE3 ex vivo. In ApoE4 astrocytes, the greater levels of LTB4, reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) were reduced after cPLA2 inhibition. CONCLUSIONS: Our findings implicate greater activation of cPLA2 signaling system with APOE4, which could represent a potential drug target for mitigating the increased neuroinflammation with APOE4 and AD.

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Published In

Mol Neurodegener

DOI

EISSN

1750-1326

Publication Date

June 15, 2022

Volume

17

Issue

1

Start / End Page

42

Location

England

Related Subject Headings

  • Synaptosomes
  • Phospholipases A2, Cytosolic
  • Oxidative Stress
  • Neurology & Neurosurgery
  • Neuroinflammatory Diseases
  • Mice, Transgenic
  • Mice
  • Leukotriene B4
  • Humans
  • Group IV Phospholipases A2
 

Citation

APA
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ICMJE
MLA
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Wang, S., Li, B., Solomon, V., Fonteh, A., Rapoport, S. I., Bennett, D. A., … Yassine, H. N. (2022). Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4. Mol Neurodegener, 17(1), 42. https://doi.org/10.1186/s13024-022-00549-5
Wang, Shaowei, Boyang Li, Victoria Solomon, Alfred Fonteh, Stanley I. Rapoport, David A. Bennett, Zoe Arvanitakis, Helena C. Chui, Patrick M. Sullivan, and Hussein N. Yassine. “Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.Mol Neurodegener 17, no. 1 (June 15, 2022): 42. https://doi.org/10.1186/s13024-022-00549-5.
Wang S, Li B, Solomon V, Fonteh A, Rapoport SI, Bennett DA, et al. Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4. Mol Neurodegener. 2022 Jun 15;17(1):42.
Wang, Shaowei, et al. “Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.Mol Neurodegener, vol. 17, no. 1, June 2022, p. 42. Pubmed, doi:10.1186/s13024-022-00549-5.
Wang S, Li B, Solomon V, Fonteh A, Rapoport SI, Bennett DA, Arvanitakis Z, Chui HC, Sullivan PM, Yassine HN. Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4. Mol Neurodegener. 2022 Jun 15;17(1):42.
Journal cover image

Published In

Mol Neurodegener

DOI

EISSN

1750-1326

Publication Date

June 15, 2022

Volume

17

Issue

1

Start / End Page

42

Location

England

Related Subject Headings

  • Synaptosomes
  • Phospholipases A2, Cytosolic
  • Oxidative Stress
  • Neurology & Neurosurgery
  • Neuroinflammatory Diseases
  • Mice, Transgenic
  • Mice
  • Leukotriene B4
  • Humans
  • Group IV Phospholipases A2