Omega-3 and omega-6 DPA equally inhibit the sphingosylphosphorylcholine-induced Ca2+-sensitization of vascular smooth muscle contraction via inhibiting Rho-kinase activation and translocation.
We previously reported that eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid (n-3 PUFA), effectively inhibits sphingosylphosphorylcholine (SPC)-induced Ca2+-sensitization of vascular smooth muscle (VSM) contraction which is a major cause of cardiovascular and cerebrovascular vasospasm, and EPA is utilized clinically to prevent cerebrovascular vasospasm. In this study, we clearly demonstrate that docosapentaenoic acid (DPA), which exists in two forms as omega-3 (n-3) and omega-6 (n-6) PUFA, strongly inhibits SPC-induced contraction in VSM tissue and human coronary artery smooth muscle cells (CASMCs), with little effect on Ca2+-dependent contraction. Furthermore, n-3 and n-6 DPA inhibited the activation and translocation of Rho-kinase from cytosol to cell membrane. Additionally, SPC-induced phosphorylation of myosin light chain (MLC) was inhibited in n-3 and n-6 DPA pretreated smooth muscleVSM cells and tissues. In summary, we provide direct evidence that n-3 and n-6 DPA effectively equally inhibits SPC-induced contraction by inhibiting Rho-kinase activation and translocation to the cell membrane.
Department of Molecular and Cellular Physiology, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Ying
Y
Zhang
Department of Molecular and Cellular Physiology, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Min
M
Zhang
Department of Molecular and Cellular Physiology, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Bochao
B
Lyu
Department of Molecular and Cellular Physiology, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Hiroko
H
Kishi
Department of Molecular and Cellular Physiology, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Sei
S
Kobayashi
D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000473:pathology*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000378:metabolism; D021381:Protein Transport; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D018994:Myosin Light Chains; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D054460:rho-Associated Kinases; D013110:Sphingosine; C026219:docosapentaenoic acid; D002118:Calcium