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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

Changes of differentially expressed proteins of borderline high and high groups compared with normal group
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T3: Changes of differentially expressed proteins of borderline high and high groups compared with normal group

Mentions: In quantitative study, the mean values of protein expression (represented in fold changes) from the pooled serum (3 5 samples; total = 15 samples per group) were extracted from 9 gels (3 independent experiments) (Table 3(Tab. 3)). Our findings revealed that the spot 2 of RBP4 was down-regulated upto -2.26 fold in the high cholesterol group while a lesser extent was detected in the borderline high group (-1.32 fold). The expression level of transthyretin was also reduced in borderline high group (-1.11 fold) and high group (-1.25 fold) when compared with the normal group. For the gelsolin, it was found that there were 2 isoforms separated by pI. Both isoforms were found to be decreased, particularly in the high group (1.36-1.47 fold). The expression level of complement factor B was higher in the borderline high group (+1.53 fold) and high group (+1.96 fold) than the normal group. Similar observation was also taken in the case of CD5 antigen-like protein (+1.83 fold and +2.04 fold in borderline high and high groups, respectively). Interestingly, the haptoglobin α1 chain was not detected in the normal group while high expression of protein (upto +3.24 fold) was observed in a concentration dependent manner with the level of cholesterol.


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)

Changes of differentially expressed proteins of borderline high and high groups compared with normal group
© Copyright Policy - open-access
Related In: Results  -  Collection

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

T3: Changes of differentially expressed proteins of borderline high and high groups compared with normal group
Mentions: In quantitative study, the mean values of protein expression (represented in fold changes) from the pooled serum (3 5 samples; total = 15 samples per group) were extracted from 9 gels (3 independent experiments) (Table 3(Tab. 3)). Our findings revealed that the spot 2 of RBP4 was down-regulated upto -2.26 fold in the high cholesterol group while a lesser extent was detected in the borderline high group (-1.32 fold). The expression level of transthyretin was also reduced in borderline high group (-1.11 fold) and high group (-1.25 fold) when compared with the normal group. For the gelsolin, it was found that there were 2 isoforms separated by pI. Both isoforms were found to be decreased, particularly in the high group (1.36-1.47 fold). The expression level of complement factor B was higher in the borderline high group (+1.53 fold) and high group (+1.96 fold) than the normal group. Similar observation was also taken in the case of CD5 antigen-like protein (+1.83 fold and +2.04 fold in borderline high and high groups, respectively). Interestingly, the haptoglobin α1 chain was not detected in the normal group while high expression of protein (upto +3.24 fold) was observed in a concentration dependent manner with the level of cholesterol.

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