Open Access

Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells

  • Authors:
    • Noriko Ishihara
    • Sawako Suzuki
    • Shou Tanaka
    • Yasuhiro Watanabe
    • Daiji Nagayama
    • Atsuhito Saiki
    • Tomoaki Tanaka
    • Ichiro Tatsuno
  • View Affiliations

  • Published online on: August 2, 2017     https://doi.org/10.3892/mmr.2017.7141
  • Pages: 4756-4762
  • Copyright: © Ishihara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Numerous clinical studies have reported that statins increase the plasma concentration of arachidonic acid, which is an ω-6 long-chain polyunsaturated fatty acid (LCPUFA), and decrease the concentrations of eicosapentaenoic acid and docosahexaenoic acid, which are ω‑3 LCPUFAs. These findings indicate that statins may affect the endogenous synthesis of LCPUFAs, which is regulated by fatty acid desaturases (FADSs) and elongation of very long‑chain fatty acids proteins (ELOVLs). The present study aimed to investigate the roles of the intrinsic mevalonate cascade and Rho‑dependent pathway in statin‑induced regulation of these desaturases and elongases, as well as cell viability using mouse 3T3‑L1 cells. mRNA expression was analyzed by quantitative polymerase chain reaction. Treatment with atorvastatin decreased cell viability and increased the mRNA expression levels of Fads1, Fads2 and ELOVL fatty acid elongase 5 (Elovl5) in a dose‑dependent manner. Mevalonate and geranylgeranyl pyrophosphate (GGPP), but not cholesterol, fully reversed the atorvastatin‑induced downregulation of cell viability and upregulation of gene expression; however, mevalonate itself did not affect cell viability and gene expression. The Rho‑associated protein kinase inhibitor Y‑27632 inhibited the mevalonate‑ and GGPP‑mediated reversal of atorvastatin‑induced upregulation of Fads1, Fads2 and Elovl5. These findings indicated that statins may affect the endogenous synthesis of LCPUFAs by regulating Fads1, Fads2 and Elovl5 gene expression via the GGPP‑dependent Rho kinase pathway in mouse 3T3-L1 cells.

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October-2017
Volume 16 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Ishihara N, Suzuki S, Tanaka S, Watanabe Y, Nagayama D, Saiki A, Tanaka T and Tatsuno I: Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells. Mol Med Rep 16: 4756-4762, 2017.
APA
Ishihara, N., Suzuki, S., Tanaka, S., Watanabe, Y., Nagayama, D., Saiki, A. ... Tatsuno, I. (2017). Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells. Molecular Medicine Reports, 16, 4756-4762. https://doi.org/10.3892/mmr.2017.7141
MLA
Ishihara, N., Suzuki, S., Tanaka, S., Watanabe, Y., Nagayama, D., Saiki, A., Tanaka, T., Tatsuno, I."Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells". Molecular Medicine Reports 16.4 (2017): 4756-4762.
Chicago
Ishihara, N., Suzuki, S., Tanaka, S., Watanabe, Y., Nagayama, D., Saiki, A., Tanaka, T., Tatsuno, I."Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells". Molecular Medicine Reports 16, no. 4 (2017): 4756-4762. https://doi.org/10.3892/mmr.2017.7141