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Retinol-binding protein 4 and its potential roles in hypercholesterolemia revealed by proteomics.

Jugnam-Ang W, Pannengpetch S, Isarankura-Na-Ayudhya P, Thippakorn C, Isarankura-Na-Ayudhya C, Lawung R, Prachayasittiku V - EXCLI J (2015)

Bottom Line: Confirmation by Western blotting revealed a significant reduction of RBP4 (approximately 50 %) in individual samples derived from the high group.Presumptive conclusion can be drawn that down-regulation of RBP4 might be attributable to the inflammation of adipocytes caused by the release of proinflammatory cytokines (e.g. tumor necrosis factor α and interleukin-1β) from adipose tissues.However, the mechanism of gelsolin reduction remains unclear.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT
Effects of hypercholesterolemia on alterations of serum proteins have not been fully elucidated. Herein, using two-dimensional gel electrophoresis (2-DE) in conjunction with LC-MS searching has successfully been carried out to investigate the change of protein expression profiles as consequences of raised blood cholesterol at different levels (normal group: total cholesterol 200 mg/dL; borderline high group: total cholesterol 200-239 mg/dL; and high group: total cholesterol ≥ 240 mg/dL) (n = 45). Results revealed that down-regulation of retinol-binding protein 4 (RBP4) (-2.26 fold), transthyretin (-1.25 fold) and gelsolin (-1.47 fold) was observed in the high group. Meanwhile, the other proteins such as haptoglobin, complement factor B and CD5 antigen-like protein were up-regulated upto +3.24, +1.96 and +2.04 fold, respectively. Confirmation by Western blotting revealed a significant reduction of RBP4 (approximately 50 %) in individual samples derived from the high group. Presumptive conclusion can be drawn that down-regulation of RBP4 might be attributable to the inflammation of adipocytes caused by the release of proinflammatory cytokines (e.g. tumor necrosis factor α and interleukin-1β) from adipose tissues. Moreover, the decrease of transthyretin might also be taken into accounts since it is known that the transthyretin usually forms complex with RBP4 to prevent glomerular filtration and excretion through the kidney. The suppressing effect on RBP4 should be potentiated by the increase of complement factor B and CD5 antigen-like protein, which rendered the adipose tissues to overwhelm the liberation of RBP4 to blood circulation by metabolic and inflammatory processes. Such inflammation could further modulate the induction of cytokine release (e.g. IL-6 and IL-1β), resulting in the synthesis of acute phase protein, in particular, haptoglobin and C-reactive proteins from hepatocytes. However, the mechanism of gelsolin reduction remains unclear. Among these differentially expressed proteins, the RBP4 has been proposed as a major linkage between hypercholesterolemia, adipose tissues, liver and kidney, which is believed to be a potential biomarker for metabolic and cardiovascular disorders associated with dyslipidemia in the future.

No MeSH data available.


Related in: MedlinePlus

Plausible association of hypercholesterolemia and other human serum proteins and their roles in adipose tissues, liver, kidney and blood circulation
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Figure 5: Plausible association of hypercholesterolemia and other human serum proteins and their roles in adipose tissues, liver, kidney and blood circulation

Mentions: Herein, proteomics approach has successfully been applied to investigate the differential expression of serum protein under different levels of hypercholesterolemia. Results revealed that six protein spots from two-dimensional gel electrophoresis (2-DE) showed different expression levels in accordance with the levels of total cholesterol (Figures 2(Fig. 2) and 3(Fig. 3)). After protein identification by ESI-Ion trap-MS (Table 2(Tab. 2)), the function of these six proteins involved in lipid metabolism, inflammation, and immune responses. Three proteins, retinol-binding protein 4 (RBP4), transthyretin (TTR) and gelsolin, were lower in borderline high and high groups than that of the normal group (Figure 3a-c(Fig. 3), Table 3(Tab. 3)). While, expression of haptoglobin, complement factor B (CFB) and CD5 antigen-like protein (CD5L) were higher in borderline high and high groups than that of the normal group (Figure 3d-f(Fig. 3), Table 3(Tab. 3)). Plausible mechanisms of alterations of these serum proteins as consequences of hypercholesterolemia have been schematically depicted in Figure 5(Fig. 5) and summarised as follows.


Retinol-binding protein 4 and its potential roles in hypercholesterolemia revealed by proteomics.

Jugnam-Ang W, Pannengpetch S, Isarankura-Na-Ayudhya P, Thippakorn C, Isarankura-Na-Ayudhya C, Lawung R, Prachayasittiku V - EXCLI J (2015)

Plausible association of hypercholesterolemia and other human serum proteins and their roles in adipose tissues, liver, kidney and blood circulation
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834671&req=5

Figure 5: Plausible association of hypercholesterolemia and other human serum proteins and their roles in adipose tissues, liver, kidney and blood circulation
Mentions: Herein, proteomics approach has successfully been applied to investigate the differential expression of serum protein under different levels of hypercholesterolemia. Results revealed that six protein spots from two-dimensional gel electrophoresis (2-DE) showed different expression levels in accordance with the levels of total cholesterol (Figures 2(Fig. 2) and 3(Fig. 3)). After protein identification by ESI-Ion trap-MS (Table 2(Tab. 2)), the function of these six proteins involved in lipid metabolism, inflammation, and immune responses. Three proteins, retinol-binding protein 4 (RBP4), transthyretin (TTR) and gelsolin, were lower in borderline high and high groups than that of the normal group (Figure 3a-c(Fig. 3), Table 3(Tab. 3)). While, expression of haptoglobin, complement factor B (CFB) and CD5 antigen-like protein (CD5L) were higher in borderline high and high groups than that of the normal group (Figure 3d-f(Fig. 3), Table 3(Tab. 3)). Plausible mechanisms of alterations of these serum proteins as consequences of hypercholesterolemia have been schematically depicted in Figure 5(Fig. 5) and summarised as follows.

Bottom Line: Confirmation by Western blotting revealed a significant reduction of RBP4 (approximately 50 %) in individual samples derived from the high group.Presumptive conclusion can be drawn that down-regulation of RBP4 might be attributable to the inflammation of adipocytes caused by the release of proinflammatory cytokines (e.g. tumor necrosis factor α and interleukin-1β) from adipose tissues.However, the mechanism of gelsolin reduction remains unclear.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT
Effects of hypercholesterolemia on alterations of serum proteins have not been fully elucidated. Herein, using two-dimensional gel electrophoresis (2-DE) in conjunction with LC-MS searching has successfully been carried out to investigate the change of protein expression profiles as consequences of raised blood cholesterol at different levels (normal group: total cholesterol 200 mg/dL; borderline high group: total cholesterol 200-239 mg/dL; and high group: total cholesterol ≥ 240 mg/dL) (n = 45). Results revealed that down-regulation of retinol-binding protein 4 (RBP4) (-2.26 fold), transthyretin (-1.25 fold) and gelsolin (-1.47 fold) was observed in the high group. Meanwhile, the other proteins such as haptoglobin, complement factor B and CD5 antigen-like protein were up-regulated upto +3.24, +1.96 and +2.04 fold, respectively. Confirmation by Western blotting revealed a significant reduction of RBP4 (approximately 50 %) in individual samples derived from the high group. Presumptive conclusion can be drawn that down-regulation of RBP4 might be attributable to the inflammation of adipocytes caused by the release of proinflammatory cytokines (e.g. tumor necrosis factor α and interleukin-1β) from adipose tissues. Moreover, the decrease of transthyretin might also be taken into accounts since it is known that the transthyretin usually forms complex with RBP4 to prevent glomerular filtration and excretion through the kidney. The suppressing effect on RBP4 should be potentiated by the increase of complement factor B and CD5 antigen-like protein, which rendered the adipose tissues to overwhelm the liberation of RBP4 to blood circulation by metabolic and inflammatory processes. Such inflammation could further modulate the induction of cytokine release (e.g. IL-6 and IL-1β), resulting in the synthesis of acute phase protein, in particular, haptoglobin and C-reactive proteins from hepatocytes. However, the mechanism of gelsolin reduction remains unclear. Among these differentially expressed proteins, the RBP4 has been proposed as a major linkage between hypercholesterolemia, adipose tissues, liver and kidney, which is believed to be a potential biomarker for metabolic and cardiovascular disorders associated with dyslipidemia in the future.

No MeSH data available.


Related in: MedlinePlus