Heart-Type Fatty Acid Binding Protein Binds Long-Chain Acylcarnitines and Protects against Lipotoxicity.

FABP3 fatty acids heart-type fatty acid-binding protein isothermal titration calorimetry long-chain acylcarnitines nuclear magnetic resonance palmitate palmitoylcarnitine

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
14 Mar 2023
Historique:
received: 21 02 2023
revised: 10 03 2023
accepted: 11 03 2023
medline: 30 3 2023
entrez: 29 3 2023
pubmed: 30 3 2023
Statut: epublish

Résumé

Heart-type fatty-acid binding protein (FABP3) is an essential cytosolic lipid transport protein found in cardiomyocytes. FABP3 binds fatty acids (FAs) reversibly and with high affinity. Acylcarnitines (ACs) are an esterified form of FAs that play an important role in cellular energy metabolism. However, an increased concentration of ACs can exert detrimental effects on cardiac mitochondria and lead to severe cardiac damage. In the present study, we evaluated the ability of FABP3 to bind long-chain ACs (LCACs) and protect cells from their harmful effects. We characterized the novel binding mechanism between FABP3 and LCACs by a cytotoxicity assay, nuclear magnetic resonance, and isothermal titration calorimetry. Our data demonstrate that FABP3 is capable of binding both FAs and LCACs as well as decreasing the cytotoxicity of LCACs. Our findings reveal that LCACs and FAs compete for the binding site of FABP3. Thus, the protective mechanism of FABP3 is found to be concentration dependent.

Identifiants

pubmed: 36982599
pii: ijms24065528
doi: 10.3390/ijms24065528
pmc: PMC10058761
pii:
doi:

Substances chimiques

acylcarnitine 0
Fatty Acid Binding Protein 3 0
Fatty Acid-Binding Proteins 0
Fatty Acids 0
Carnitine S7UI8SM58A

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : European Union's Horizon 2020 research and innovation program project FAT4BRAIN
ID : 857394
Organisme : Latvian Institute of Organic Synthesis
ID : IG-2023-04

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Auteurs

Diana Zelencova-Gopejenko (D)

Department of Physical Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.
Faculty of Materials Science and Applied Chemistry, Riga Technical University, Paula Valdena 3, LV-1048 Riga, Latvia.

Melita Videja (M)

Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.
Faculty of Pharmacy, Rīga Stradinš University, Dzirciema 16, LV-1007 Riga, Latvia.

Aiga Grandane (A)

Organic Synthesis Group, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.

Linda Pudnika-Okinčica (L)

Organic Synthesis Group, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.

Anda Sipola (A)

Laboratory of Membrane Active Compounds and β-Diketones, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.

Karlis Vilks (K)

Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.

Maija Dambrova (M)

Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.
Faculty of Pharmacy, Rīga Stradinš University, Dzirciema 16, LV-1007 Riga, Latvia.

Kristaps Jaudzems (K)

Department of Physical Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.

Edgars Liepinsh (E)

Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.

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