Rosuvastatin modulates the post-translational acetylome in endothelial cells

Ming Chung Lin, Chung Hsi Hsing, Fu An Li, Chien Hsing Wu, Yaw Syan Fu, Jen Kun Cheng, Bin Huang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Statins are lipid-lowering drugs that can simultaneously evoke pleiotropic effects on cardioprotection, vasodilation, and diabetes prevention. Recently, statins have been reported to be able to activate the AMP-activated protein kinase, thereby up-regulating sirtuin (SIRT) that functions as non-histone deacetylases. Therefore, it is essential to investigate the post-translational acetylome that might explain the mechanism of statin-modulated pleiotropic effects. Method: Endothelial cells EAhy 926 treated with rosuvastatin were used to monitor the expression of SIRTs proteins. The protein lysates of both mock- and rosuvastatin-treated cells were further separated by two-dimensional gel electrophoresis coupled with western blotting analysis. The significantly changed acetylcontaining proteins detected by using an anti-acetyl lysine antibody were collected from another preparative gel for mass spectrometric assay to identify the acetylated site in the proteins. Results: Rosuvastatin treatment was shown to increase the SIRT1 expression when compared with SIRT2. Among 100 detected proteins with acetylated signal, 12 showed an increased level of acetylation, whereas 6 showed a decreased level of acetylation (deacetylation). The acetylated lysine (K) sites of 3 heat shock proteins, i.e., HSP47/K165, HSP70/K380, and heat shock-inducible protein/K417, were determined.We also found that beta-filamin, elongation factor, galectin and hCG22067 have 2 acetylated lysine sites in their peptide sequences. These dynamic acetylations might alter the protein's function and are thought to be important in regulating statin-mediated pleiotropic effect. Conclusions: Our study provided a feasible methodology for detecting acetylated proteins. This acetylome information may be utilized to explain, at least partially, the mechanisms of statin-derived pleiotropic effects.

Original languageEnglish
Pages (from-to)67-73
Number of pages7
JournalActa Cardiologica Sinica
Volume30
Issue number1
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Endothelial Cells
Acetylation
Proteins
Lysine
HSP47 Heat-Shock Proteins
Filamins
Galectins
Peptide Elongation Factors
AMP-Activated Protein Kinases
Electrophoresis, Gel, Two-Dimensional
Heat-Shock Proteins
Rosuvastatin Calcium
Vasodilation
Western Blotting
Gels
Lipids
Peptides
Antibodies
Pharmaceutical Preparations

Keywords

  • Acetylation/deacetylation
  • Acetylome
  • Endothelial cell
  • Proteomics
  • Rosuvastatin
  • Sirtuin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lin, M. C., Hsing, C. H., Li, F. A., Wu, C. H., Fu, Y. S., Cheng, J. K., & Huang, B. (2014). Rosuvastatin modulates the post-translational acetylome in endothelial cells. Acta Cardiologica Sinica, 30(1), 67-73.

Rosuvastatin modulates the post-translational acetylome in endothelial cells. / Lin, Ming Chung; Hsing, Chung Hsi; Li, Fu An; Wu, Chien Hsing; Fu, Yaw Syan; Cheng, Jen Kun; Huang, Bin.

In: Acta Cardiologica Sinica, Vol. 30, No. 1, 2014, p. 67-73.

Research output: Contribution to journalArticle

Lin, MC, Hsing, CH, Li, FA, Wu, CH, Fu, YS, Cheng, JK & Huang, B 2014, 'Rosuvastatin modulates the post-translational acetylome in endothelial cells', Acta Cardiologica Sinica, vol. 30, no. 1, pp. 67-73.
Lin MC, Hsing CH, Li FA, Wu CH, Fu YS, Cheng JK et al. Rosuvastatin modulates the post-translational acetylome in endothelial cells. Acta Cardiologica Sinica. 2014;30(1):67-73.
Lin, Ming Chung ; Hsing, Chung Hsi ; Li, Fu An ; Wu, Chien Hsing ; Fu, Yaw Syan ; Cheng, Jen Kun ; Huang, Bin. / Rosuvastatin modulates the post-translational acetylome in endothelial cells. In: Acta Cardiologica Sinica. 2014 ; Vol. 30, No. 1. pp. 67-73.
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abstract = "Background: Statins are lipid-lowering drugs that can simultaneously evoke pleiotropic effects on cardioprotection, vasodilation, and diabetes prevention. Recently, statins have been reported to be able to activate the AMP-activated protein kinase, thereby up-regulating sirtuin (SIRT) that functions as non-histone deacetylases. Therefore, it is essential to investigate the post-translational acetylome that might explain the mechanism of statin-modulated pleiotropic effects. Method: Endothelial cells EAhy 926 treated with rosuvastatin were used to monitor the expression of SIRTs proteins. The protein lysates of both mock- and rosuvastatin-treated cells were further separated by two-dimensional gel electrophoresis coupled with western blotting analysis. The significantly changed acetylcontaining proteins detected by using an anti-acetyl lysine antibody were collected from another preparative gel for mass spectrometric assay to identify the acetylated site in the proteins. Results: Rosuvastatin treatment was shown to increase the SIRT1 expression when compared with SIRT2. Among 100 detected proteins with acetylated signal, 12 showed an increased level of acetylation, whereas 6 showed a decreased level of acetylation (deacetylation). The acetylated lysine (K) sites of 3 heat shock proteins, i.e., HSP47/K165, HSP70/K380, and heat shock-inducible protein/K417, were determined.We also found that beta-filamin, elongation factor, galectin and hCG22067 have 2 acetylated lysine sites in their peptide sequences. These dynamic acetylations might alter the protein's function and are thought to be important in regulating statin-mediated pleiotropic effect. Conclusions: Our study provided a feasible methodology for detecting acetylated proteins. This acetylome information may be utilized to explain, at least partially, the mechanisms of statin-derived pleiotropic effects.",
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AU - Lin, Ming Chung

AU - Hsing, Chung Hsi

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AU - Wu, Chien Hsing

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AU - Cheng, Jen Kun

AU - Huang, Bin

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N2 - Background: Statins are lipid-lowering drugs that can simultaneously evoke pleiotropic effects on cardioprotection, vasodilation, and diabetes prevention. Recently, statins have been reported to be able to activate the AMP-activated protein kinase, thereby up-regulating sirtuin (SIRT) that functions as non-histone deacetylases. Therefore, it is essential to investigate the post-translational acetylome that might explain the mechanism of statin-modulated pleiotropic effects. Method: Endothelial cells EAhy 926 treated with rosuvastatin were used to monitor the expression of SIRTs proteins. The protein lysates of both mock- and rosuvastatin-treated cells were further separated by two-dimensional gel electrophoresis coupled with western blotting analysis. The significantly changed acetylcontaining proteins detected by using an anti-acetyl lysine antibody were collected from another preparative gel for mass spectrometric assay to identify the acetylated site in the proteins. Results: Rosuvastatin treatment was shown to increase the SIRT1 expression when compared with SIRT2. Among 100 detected proteins with acetylated signal, 12 showed an increased level of acetylation, whereas 6 showed a decreased level of acetylation (deacetylation). The acetylated lysine (K) sites of 3 heat shock proteins, i.e., HSP47/K165, HSP70/K380, and heat shock-inducible protein/K417, were determined.We also found that beta-filamin, elongation factor, galectin and hCG22067 have 2 acetylated lysine sites in their peptide sequences. These dynamic acetylations might alter the protein's function and are thought to be important in regulating statin-mediated pleiotropic effect. Conclusions: Our study provided a feasible methodology for detecting acetylated proteins. This acetylome information may be utilized to explain, at least partially, the mechanisms of statin-derived pleiotropic effects.

AB - Background: Statins are lipid-lowering drugs that can simultaneously evoke pleiotropic effects on cardioprotection, vasodilation, and diabetes prevention. Recently, statins have been reported to be able to activate the AMP-activated protein kinase, thereby up-regulating sirtuin (SIRT) that functions as non-histone deacetylases. Therefore, it is essential to investigate the post-translational acetylome that might explain the mechanism of statin-modulated pleiotropic effects. Method: Endothelial cells EAhy 926 treated with rosuvastatin were used to monitor the expression of SIRTs proteins. The protein lysates of both mock- and rosuvastatin-treated cells were further separated by two-dimensional gel electrophoresis coupled with western blotting analysis. The significantly changed acetylcontaining proteins detected by using an anti-acetyl lysine antibody were collected from another preparative gel for mass spectrometric assay to identify the acetylated site in the proteins. Results: Rosuvastatin treatment was shown to increase the SIRT1 expression when compared with SIRT2. Among 100 detected proteins with acetylated signal, 12 showed an increased level of acetylation, whereas 6 showed a decreased level of acetylation (deacetylation). The acetylated lysine (K) sites of 3 heat shock proteins, i.e., HSP47/K165, HSP70/K380, and heat shock-inducible protein/K417, were determined.We also found that beta-filamin, elongation factor, galectin and hCG22067 have 2 acetylated lysine sites in their peptide sequences. These dynamic acetylations might alter the protein's function and are thought to be important in regulating statin-mediated pleiotropic effect. Conclusions: Our study provided a feasible methodology for detecting acetylated proteins. This acetylome information may be utilized to explain, at least partially, the mechanisms of statin-derived pleiotropic effects.

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