4-Hydroxynonenal Modulates Blood–Brain Barrier Permeability In Vitro through Changes in Lipid Composition and Oxidative Status of Endothelial Cells and Astrocytes

Scientific paper - Original scientific paper

• Author: Marina Cindrić
• Author: Ana Čipak Gašparović
• Author: Lidija Milković
• Author: Ivana Tartaro Bujak
• Author: Branka Mihaljević
• Author: Neven Žarković
• Author: Kamelija Žarković
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE

Abstract (english)

Blood brain barrier (BBB) is a dynamic interface responsible for proper functioning of brain, but also a major obstacle for effective treatment of neurological diseases. Increased levels of free radicals, in high ferrous and high lipid content surrounding, induce lipid peroxidation, leading to production of 4-hydroxynonenal (HNE). HNE modifies all key proteins responsible for proper brain functioning thus playing a major role in the onset of neurological diseases. To investigate HNE effects on BBB permeability, we developed two in vitro BBB models–‘physiological’ and ‘pathological’. The latter mimicked HNE modified extracellular matrix under oxidative stress conditions in brain pathologies. We showed that exogenous HNE induce activation of antioxidative defense systems by increasing catalase activity and glutathione content as well as reducing lipid peroxide levels in endothelial cells and astrocytes of ‘physiological’ model. While in ‘pathological’ model, exogenous HNE further increased lipid peroxidation levels of endothelial cells and astrocytes, followed by increase in Nrf2 and glutathione levels in endothelial cells. At lipid composition level, HNE caused increase in ω3 polyunsaturated fatty acid (PUFA) level in endothelial cells, followed by decrease in ω3 PUFA level and increase in monounsaturated fatty acid level in astrocytes. Using these models, we showed for the first time that HNE in ‘pathological’ model can reduce BBB permeability.

• Keywords (english): Antioxidants / metabolism; Astrocytes / metabolism; Blood-Brain Barrier / metabolism; Endothelial Cells / metabolism; Glutathione / metabolism; Lipid Peroxides; Oxidative Stress / physiology; Permeability
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: International Journal of Molecular Sciences
• Numbering: vol. 23, no. 22, 14373
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms232214373
• URN:NBN: urn:nbn:hr:105:170700
• Publication: 2022-11-19
• Project: Number: 108-0000000-0028; Title (croatian): Oksidacijski stres i tumori središnjeg živčanog sustava; Title (english): Oxidative stress and central nervous system tumors; Leader: Kamelija Žarković; Jurisdiction: Croatia; Funding stream: ZP
• Project: Number: 098-0982464-2519; Title (croatian): Lipidi, slobodni radikali i njihovi glasnici u integrativnoj onkologiji; Title (english): Lipids, free radicals and their messengers in integrative oncology; Leader: Neven Žarković; Jurisdiction: Croatia; Funding stream: ZP
• Document URL: https://www.mdpi.com/1422-0067/23/22/14373
• Type of resource: Text
• Access conditions: Open access
• Created on: 2023-06-13 11:02:43