TY - JOUR
T1 - Heart-Type Fatty Acid Binding Protein Binds Long-Chain Acylcarnitines and Protects against Lipotoxicity
AU - Zelencova-Gopejenko, Diana
AU - Videja, Melita
AU - Grandane, Aiga
AU - Pudnika-Okinčica, Linda
AU - Sipola, Anda
AU - Vilks, Karlis
AU - Dambrova, Maija
AU - Jaudzems, Kristaps
AU - Liepinsh, Edgars
N1 - Funding Information:
This research was funded by the European Union’s Horizon 2020 research and innovation program project FAT4BRAIN under grant agreement No. 857394 and by Latvian Institute of Organic Synthesis internal student grants IG-2022-04 and IG-2023-04 (to D.Z.-G.).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/3/14
Y1 - 2023/3/14
N2 - 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.
AB - 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.
KW - Fatty Acid Binding Protein 3/metabolism
KW - Fatty Acid-Binding Proteins/metabolism
KW - Fatty Acids pharmacology
KW - Carnitine
KW - Myocytes
KW - Cardiac metabolism
KW - isothermal titration calorimetry
KW - long-chain acylcarnitines
UR - http://www.scopus.com/inward/record.url?scp=85151108933&partnerID=8YFLogxK
U2 - 10.3390/ijms24065528
DO - 10.3390/ijms24065528
M3 - Article
C2 - 36982599
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 6
M1 - 5528
ER -