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Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis.

Xu W, Cardenes N, Corey C, Erzurum SC, Shiva S - PLoS ONE (2015)

Bottom Line: Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic.However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients.The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients.

View Article: PubMed Central - PubMed

Affiliation: Lerner Research Institute, Cleveland, Ohio, United States of America.

ABSTRACT
Asthma, a chronic inflammatory airway disease, is typified by high levels of TH2-cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma.

No MeSH data available.


Related in: MedlinePlus

Greater TCA Cycle Activity in Asthma.(A) ATP content in control (white bars) and asthmatic (black bars) individuals basally and after inhibition of glycolysis by 2-DG. (B) Western analyses of aconitase expression in platelets. Asthmatic individials (lanes 4−6) had similar aconitase protein expression in platelets to healthy controls (lanes 1−3) by western blot. (C) Activity of aconitase, succinate dehydrogenase and citrate synthase in platelets from asthmatics (black bars) as a fold change of the activity of control platelets (white bars). n = 13 controls, n = 10 asthmatics. *p<0.01; #p<0.05.
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pone.0132007.g005: Greater TCA Cycle Activity in Asthma.(A) ATP content in control (white bars) and asthmatic (black bars) individuals basally and after inhibition of glycolysis by 2-DG. (B) Western analyses of aconitase expression in platelets. Asthmatic individials (lanes 4−6) had similar aconitase protein expression in platelets to healthy controls (lanes 1−3) by western blot. (C) Activity of aconitase, succinate dehydrogenase and citrate synthase in platelets from asthmatics (black bars) as a fold change of the activity of control platelets (white bars). n = 13 controls, n = 10 asthmatics. *p<0.01; #p<0.05.

Mentions: ATP content in platelets from asthma (87.43 ± 4.61 pmol/106 platelets; n = 7) was not significantly different from controls (84.37 ± 5.32 pmol/106 platelets; n = 8; P = 0.8). However, ATP content in the presence of glycolytic inhibition was greater in platelets from asthmatics (69.12 ± 2.51 pmol/106 platelets; n = 7) than controls (62.71 ± 1.54 pmol/106 platelets, P = 0.04). These data indicate less glycolytic-reliance for cellular respiration in asthma (Fig 5A).


Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis.

Xu W, Cardenes N, Corey C, Erzurum SC, Shiva S - PLoS ONE (2015)

Greater TCA Cycle Activity in Asthma.(A) ATP content in control (white bars) and asthmatic (black bars) individuals basally and after inhibition of glycolysis by 2-DG. (B) Western analyses of aconitase expression in platelets. Asthmatic individials (lanes 4−6) had similar aconitase protein expression in platelets to healthy controls (lanes 1−3) by western blot. (C) Activity of aconitase, succinate dehydrogenase and citrate synthase in platelets from asthmatics (black bars) as a fold change of the activity of control platelets (white bars). n = 13 controls, n = 10 asthmatics. *p<0.01; #p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4492492&req=5

pone.0132007.g005: Greater TCA Cycle Activity in Asthma.(A) ATP content in control (white bars) and asthmatic (black bars) individuals basally and after inhibition of glycolysis by 2-DG. (B) Western analyses of aconitase expression in platelets. Asthmatic individials (lanes 4−6) had similar aconitase protein expression in platelets to healthy controls (lanes 1−3) by western blot. (C) Activity of aconitase, succinate dehydrogenase and citrate synthase in platelets from asthmatics (black bars) as a fold change of the activity of control platelets (white bars). n = 13 controls, n = 10 asthmatics. *p<0.01; #p<0.05.
Mentions: ATP content in platelets from asthma (87.43 ± 4.61 pmol/106 platelets; n = 7) was not significantly different from controls (84.37 ± 5.32 pmol/106 platelets; n = 8; P = 0.8). However, ATP content in the presence of glycolytic inhibition was greater in platelets from asthmatics (69.12 ± 2.51 pmol/106 platelets; n = 7) than controls (62.71 ± 1.54 pmol/106 platelets, P = 0.04). These data indicate less glycolytic-reliance for cellular respiration in asthma (Fig 5A).

Bottom Line: Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic.However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients.The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients.

View Article: PubMed Central - PubMed

Affiliation: Lerner Research Institute, Cleveland, Ohio, United States of America.

ABSTRACT
Asthma, a chronic inflammatory airway disease, is typified by high levels of TH2-cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma.

No MeSH data available.


Related in: MedlinePlus