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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

Down- and up-regulation of the changed proteins (a-f) found in normal, borderline high, and high total cholesterol groups
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Figure 3: Down- and up-regulation of the changed proteins (a-f) found in normal, borderline high, and high total cholesterol groups

Mentions: CD5 antigen-like protein (spot no. 11) were differentially expressed. In zoomed gels, it is noteworthy that the retinol-binding protein 4 exists as two spots at the same pI (~5.7) with differences in molecular weight (designated as spots 1 and 2 for the higher and lower molecular weight, respectively) (Figure 3(Fig. 3)). The presence of these two isoforms was in consistency with previous studies (Cubedo, Padro, Cinca, Mata, Alonso and Badimon, 2014[13]). From our findings, three proteins (spot 2 of RBP4, transthyretin and gelsolin) were down-regulated while the others (spot 1 of RBP4, haptoglobin α 1 chain, complement factor B and CD5 antigen-like protein) were up-regulated when compared with those found in the normal group.


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)

Down- and up-regulation of the changed proteins (a-f) found in normal, borderline high, and high total cholesterol groups
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Down- and up-regulation of the changed proteins (a-f) found in normal, borderline high, and high total cholesterol groups
Mentions: CD5 antigen-like protein (spot no. 11) were differentially expressed. In zoomed gels, it is noteworthy that the retinol-binding protein 4 exists as two spots at the same pI (~5.7) with differences in molecular weight (designated as spots 1 and 2 for the higher and lower molecular weight, respectively) (Figure 3(Fig. 3)). The presence of these two isoforms was in consistency with previous studies (Cubedo, Padro, Cinca, Mata, Alonso and Badimon, 2014[13]). From our findings, three proteins (spot 2 of RBP4, transthyretin and gelsolin) were down-regulated while the others (spot 1 of RBP4, haptoglobin α 1 chain, complement factor B and CD5 antigen-like protein) were up-regulated when compared with those found in the normal group.

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