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Alteration of actin dependent signaling pathways associated with membrane microdomains in hyperlipidemia.

Suica VI, Uyy E, Boteanu RM, Ivan L, Antohe F - Proteome Sci (2015)

Bottom Line: The findings of the study allowed the identification with high confidence of 1925 proteins, 291 of which were found significantly altered by the modified genetic background, by the statin treatment or both conditions.The statistical significant over-representation of Regulation of actin cytoskeleton, Focal adhesion and Adherens junction Kyoto Encyclopedia of Genes and Genomes signaling pathways was demonstrated through bioinformatics analysis.Our study provides the basis for future work probing how the protein activities at the membrane-cytoskeleton interface are dependent upon genetic induced hyperlipidemia.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu", 8 BP Hasdeu Street, PO Box 35-14, 050568 Bucharest, Romania.

ABSTRACT

Background: Membrane microdomains represent dynamic membrane nano-assemblies enriched in signaling molecules suggesting their active involvement in not only physiological but also pathological molecular processes. The hyperlipidemic stress is a major risk factor of atherosclerosis, but its exact mechanisms of action at the membrane microdomains level remain elusive. The aim of the present study was to determine whether membrane-cytoskeleton proteome in the pulmonary tissue could be modulated by the hyperlipidemic stress, a major risk factor of atherosclerosis.

Results: High resolution mass spectrometry based proteomics analysis was performed for detergent resistant membrane microdomains isolated from lung homogenates of control, ApoE deficient and statin treated ApoE deficient mice. The findings of the study allowed the identification with high confidence of 1925 proteins, 291 of which were found significantly altered by the modified genetic background, by the statin treatment or both conditions. Principal component analysis revealed a proximal partitioning of the biological replicates, but also a distinct spatial scattering of the sample groups, highlighting different quantitative profiles. The statistical significant over-representation of Regulation of actin cytoskeleton, Focal adhesion and Adherens junction Kyoto Encyclopedia of Genes and Genomes signaling pathways was demonstrated through bioinformatics analysis. The three inter-relation maps comprised 29 of regulated proteins, proving membrane-cytoskeleton coupling targeting and alteration by hyperlipidemia and/or statin treatment.

Conclusions: The findings of the study allowed the identification with high confidence of the main proteins modulated by the hyperlipidemic stress involved in the actin-dependent pathways. Our study provides the basis for future work probing how the protein activities at the membrane-cytoskeleton interface are dependent upon genetic induced hyperlipidemia.

No MeSH data available.


Related in: MedlinePlus

Liquid chromatography – tandem mass spectrometry data. a Numerical distribution diagram showing the identified proteins in detergent resistant membrane microdomains in: control group (C: 1279 proteins), ApoE KO mice that received hyperlipidemic diet (A: 1233 proteins) and ApoE KO mice fed hyperlipidemic diet followed by statin treatment (At: 1239 proteins). Commonly identified (932 proteins) as well as uniquely attributed proteins (C: 191 proteins; A: 134 proteins and At: 160 proteins) are depicted. b The normalized ratio was plotted against the significance level for the proteins which were altered either in the hyperlipidemic condition (A/C: red circles) or the statin treatment in genetic hyperlipidemic stress (At/C: blue circles) or both of them. The horizontal line represents the minimum significance value threshold (P < 0.05), while the vertical lines denote the 1.5 fold alteration cut-off. The purple color signifies the superposition of red and blue circles. c Spatial quantitative scattering profile for the biological replicates of each group was performed for the control group (blue dots), ApoE KO mice fed hyperlipidemic diet (green dots) and ApoE KO mice that received hyperlipidemic diet followed by statin treatment (red dots)
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Fig2: Liquid chromatography – tandem mass spectrometry data. a Numerical distribution diagram showing the identified proteins in detergent resistant membrane microdomains in: control group (C: 1279 proteins), ApoE KO mice that received hyperlipidemic diet (A: 1233 proteins) and ApoE KO mice fed hyperlipidemic diet followed by statin treatment (At: 1239 proteins). Commonly identified (932 proteins) as well as uniquely attributed proteins (C: 191 proteins; A: 134 proteins and At: 160 proteins) are depicted. b The normalized ratio was plotted against the significance level for the proteins which were altered either in the hyperlipidemic condition (A/C: red circles) or the statin treatment in genetic hyperlipidemic stress (At/C: blue circles) or both of them. The horizontal line represents the minimum significance value threshold (P < 0.05), while the vertical lines denote the 1.5 fold alteration cut-off. The purple color signifies the superposition of red and blue circles. c Spatial quantitative scattering profile for the biological replicates of each group was performed for the control group (blue dots), ApoE KO mice fed hyperlipidemic diet (green dots) and ApoE KO mice that received hyperlipidemic diet followed by statin treatment (red dots)

Mentions: The DRM microdomains comparative shotgun proteomic LC-MS experiments revealed a high plethora of resident and membrane-associated proteins involved in molecular interactions and enzymatic functions. High performance nano-liquid chromatography mass spectrometry experiments were conducted for proteome characterization of isolated DRM microdomains. Thus, 1279 proteins were identified in the control (C), 1233 proteins in the atherosclerotic samples (A) and 1239 proteins came from the treated animals (At), using raw file combination for replicate samples (Fig. 2a).Fig. 2


Alteration of actin dependent signaling pathways associated with membrane microdomains in hyperlipidemia.

Suica VI, Uyy E, Boteanu RM, Ivan L, Antohe F - Proteome Sci (2015)

Liquid chromatography – tandem mass spectrometry data. a Numerical distribution diagram showing the identified proteins in detergent resistant membrane microdomains in: control group (C: 1279 proteins), ApoE KO mice that received hyperlipidemic diet (A: 1233 proteins) and ApoE KO mice fed hyperlipidemic diet followed by statin treatment (At: 1239 proteins). Commonly identified (932 proteins) as well as uniquely attributed proteins (C: 191 proteins; A: 134 proteins and At: 160 proteins) are depicted. b The normalized ratio was plotted against the significance level for the proteins which were altered either in the hyperlipidemic condition (A/C: red circles) or the statin treatment in genetic hyperlipidemic stress (At/C: blue circles) or both of them. The horizontal line represents the minimum significance value threshold (P < 0.05), while the vertical lines denote the 1.5 fold alteration cut-off. The purple color signifies the superposition of red and blue circles. c Spatial quantitative scattering profile for the biological replicates of each group was performed for the control group (blue dots), ApoE KO mice fed hyperlipidemic diet (green dots) and ApoE KO mice that received hyperlipidemic diet followed by statin treatment (red dots)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666118&req=5

Fig2: Liquid chromatography – tandem mass spectrometry data. a Numerical distribution diagram showing the identified proteins in detergent resistant membrane microdomains in: control group (C: 1279 proteins), ApoE KO mice that received hyperlipidemic diet (A: 1233 proteins) and ApoE KO mice fed hyperlipidemic diet followed by statin treatment (At: 1239 proteins). Commonly identified (932 proteins) as well as uniquely attributed proteins (C: 191 proteins; A: 134 proteins and At: 160 proteins) are depicted. b The normalized ratio was plotted against the significance level for the proteins which were altered either in the hyperlipidemic condition (A/C: red circles) or the statin treatment in genetic hyperlipidemic stress (At/C: blue circles) or both of them. The horizontal line represents the minimum significance value threshold (P < 0.05), while the vertical lines denote the 1.5 fold alteration cut-off. The purple color signifies the superposition of red and blue circles. c Spatial quantitative scattering profile for the biological replicates of each group was performed for the control group (blue dots), ApoE KO mice fed hyperlipidemic diet (green dots) and ApoE KO mice that received hyperlipidemic diet followed by statin treatment (red dots)
Mentions: The DRM microdomains comparative shotgun proteomic LC-MS experiments revealed a high plethora of resident and membrane-associated proteins involved in molecular interactions and enzymatic functions. High performance nano-liquid chromatography mass spectrometry experiments were conducted for proteome characterization of isolated DRM microdomains. Thus, 1279 proteins were identified in the control (C), 1233 proteins in the atherosclerotic samples (A) and 1239 proteins came from the treated animals (At), using raw file combination for replicate samples (Fig. 2a).Fig. 2

Bottom Line: The findings of the study allowed the identification with high confidence of 1925 proteins, 291 of which were found significantly altered by the modified genetic background, by the statin treatment or both conditions.The statistical significant over-representation of Regulation of actin cytoskeleton, Focal adhesion and Adherens junction Kyoto Encyclopedia of Genes and Genomes signaling pathways was demonstrated through bioinformatics analysis.Our study provides the basis for future work probing how the protein activities at the membrane-cytoskeleton interface are dependent upon genetic induced hyperlipidemia.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu", 8 BP Hasdeu Street, PO Box 35-14, 050568 Bucharest, Romania.

ABSTRACT

Background: Membrane microdomains represent dynamic membrane nano-assemblies enriched in signaling molecules suggesting their active involvement in not only physiological but also pathological molecular processes. The hyperlipidemic stress is a major risk factor of atherosclerosis, but its exact mechanisms of action at the membrane microdomains level remain elusive. The aim of the present study was to determine whether membrane-cytoskeleton proteome in the pulmonary tissue could be modulated by the hyperlipidemic stress, a major risk factor of atherosclerosis.

Results: High resolution mass spectrometry based proteomics analysis was performed for detergent resistant membrane microdomains isolated from lung homogenates of control, ApoE deficient and statin treated ApoE deficient mice. The findings of the study allowed the identification with high confidence of 1925 proteins, 291 of which were found significantly altered by the modified genetic background, by the statin treatment or both conditions. Principal component analysis revealed a proximal partitioning of the biological replicates, but also a distinct spatial scattering of the sample groups, highlighting different quantitative profiles. The statistical significant over-representation of Regulation of actin cytoskeleton, Focal adhesion and Adherens junction Kyoto Encyclopedia of Genes and Genomes signaling pathways was demonstrated through bioinformatics analysis. The three inter-relation maps comprised 29 of regulated proteins, proving membrane-cytoskeleton coupling targeting and alteration by hyperlipidemia and/or statin treatment.

Conclusions: The findings of the study allowed the identification with high confidence of the main proteins modulated by the hyperlipidemic stress involved in the actin-dependent pathways. Our study provides the basis for future work probing how the protein activities at the membrane-cytoskeleton interface are dependent upon genetic induced hyperlipidemia.

No MeSH data available.


Related in: MedlinePlus