Heart-Type Fatty Acid Binding Protein Binds Long-Chain Acylcarnitines and Protects against Lipotoxicity
Creators
- 1. Department of Physical Organic Chemistry, Latvian Institute of Organic Synthesis
- 2. Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis
- 3. Organic Synthesis Group, Latvian Institute of Organic Synthesis
- 4. Laboratory of Membrane Active Compounds and β-Diketones, Latvian Institute of Organic Synthesis
Description
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.
Files
ijms-24-05528.pdf
Files
(4.3 MB)
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