Lysophosphatidylcholine increases Na+/Ca2+ exchanger expression via RhoB-geranylgeranylation in H9c2 cells.
The expression levels of the Na(+)/Ca(2+) exchanger type 1 (NCX1) change under various cardiac pathophysiological conditions, but the mechanism is unknown. We previously demonstrated that lysophosphatidylcholine (LPC) increased NCX1 expression by activating RhoB in H9c2 cardiomyoblasts. Conversely, fluvastatin (Flv), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, decreased NCX1 mRNA and protein expression by inhibiting RhoB. RhoB can be isoprenylated by either geranylgeranylpyrophosphate (GGPP) or farnesylpyrophosphate (FPP). Here we investigated which of GGPP or FPP is involved in the NCX1-increasing effect of LPC. When LPC was added with GGPP to the Flv-treated H9c2 cells, NCX1 mRNA was increased to a level significantly higher than that in the control cells. Only GGPP, but not FPP, allowed LPC to increase NCX1 mRNA in the presence of Flv. Furthermore, geranylgeranyltransferase 1 inhibitor (GGTI), but not farnesyltransferase inhibitor (FTI), inhibited the LPC-induced NCX1 mRNA increase. We conclude that geranylgeranylation, but not farnesylation, of RhoB mediates LPC-induced NCX1 mRNA increase in H9c2 cells.
Department of Pharmacology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Sachiko
S
Maeda
Kazuho
K
Sakamoto
Isao
I
Matsuoka
Takahiro
T
Iwamoto
Junko
J
Kimura
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D054876:Prenylation / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D020743:rhoB GTP-Binding Protein / Q000378:metabolism*
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008244:Lysophosphatidylcholines; D011106:Polyisoprenyl Phosphates; D012333:RNA, Messenger; D012717:Sesquiterpenes; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D000077340:Fluvastatin; C004808:farnesyl pyrophosphate; D020743:rhoB GTP-Binding Protein; D002118:Calcium