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Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.

Ray S, Patel SK, Venkatesh A, Bhave A, Kumar V, Singh V, Chatterjee G, Shah VG, Sharma S, Renu D, Nafis N, Gandhe P, Gogtay N, Thatte U, Sehgal K, Verma S, Karak A, Khanra D, Talukdar A, Kochar SK, S B V, Kochar DK, Rojh D, Varma SG, Gandhi MN, Srikanth R, Patankar S, Srivastava S - Sci Rep (2016)

Bottom Line: In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure.Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection.Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

ABSTRACT
In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

No MeSH data available.


Related in: MedlinePlus

Comparative analysis of serum proteome alterations in NSVM and SVM patients.(A) Trends of a few selected differentially abundant proteins in NSVM and SVM identified in 2D-DIGE. Data are represented as standardized log abundance of spot intensity (One representative spot is shown for the proteins with multiple spots in 2D-DIGE gels). (B) Volcano plots showing P values (−log10) versus protein ratio of (log2). Red, up-regulated; Green, down-regulated; and Blue, not significantly changed (adjusted p-value > 0.05) proteins. A few selected differentially abundant proteins are labeled. (C) Representative MS/MS spectrum of a few selected differentially abundant proteins. Inset showing the iTRAQ reporter ion intensities for representative peptides in HC, NSVM and SVM. (D) Venn diagram showing the unique and common differentially abundant proteins (p-value ≤ 0.05) in NSVM and SVM identified in iTRAQ analysis by ESI-Q-TOF. (E) Venn diagram showing the unique and overlapping proteins identified in Q-Exactive and ESI-Q-TOF.
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f2: Comparative analysis of serum proteome alterations in NSVM and SVM patients.(A) Trends of a few selected differentially abundant proteins in NSVM and SVM identified in 2D-DIGE. Data are represented as standardized log abundance of spot intensity (One representative spot is shown for the proteins with multiple spots in 2D-DIGE gels). (B) Volcano plots showing P values (−log10) versus protein ratio of (log2). Red, up-regulated; Green, down-regulated; and Blue, not significantly changed (adjusted p-value > 0.05) proteins. A few selected differentially abundant proteins are labeled. (C) Representative MS/MS spectrum of a few selected differentially abundant proteins. Inset showing the iTRAQ reporter ion intensities for representative peptides in HC, NSVM and SVM. (D) Venn diagram showing the unique and common differentially abundant proteins (p-value ≤ 0.05) in NSVM and SVM identified in iTRAQ analysis by ESI-Q-TOF. (E) Venn diagram showing the unique and overlapping proteins identified in Q-Exactive and ESI-Q-TOF.

Mentions: A gel-based proteomics analysis using 2D-DIGE identified approximately 1200 protein spots on each gel in DeCyder 2D software analysis. Comparative serum proteome analysis of HC and SVM revealed differential abundance of 131 protein spots (p < 0.05), among which 75 spots exhibited increased abundance, while the remaining 56 spots were down-regulated (Table S2A). Comparative analysis of NSVM and SVM indicated differential abundance of 26 protein spots, among which 20 were up-regulated and 6 were down-regulated (Table S2B). Identity of 22 protein spots (10 up-regulated and 12 down-regulated) was established by subsequent MALDI-TOF/TOF MS analysis (Table S3). Graphical representations for differential abundance of some selected proteins in NSVM and SVM are shown in Fig. 2A.


Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.

Ray S, Patel SK, Venkatesh A, Bhave A, Kumar V, Singh V, Chatterjee G, Shah VG, Sharma S, Renu D, Nafis N, Gandhe P, Gogtay N, Thatte U, Sehgal K, Verma S, Karak A, Khanra D, Talukdar A, Kochar SK, S B V, Kochar DK, Rojh D, Varma SG, Gandhi MN, Srikanth R, Patankar S, Srivastava S - Sci Rep (2016)

Comparative analysis of serum proteome alterations in NSVM and SVM patients.(A) Trends of a few selected differentially abundant proteins in NSVM and SVM identified in 2D-DIGE. Data are represented as standardized log abundance of spot intensity (One representative spot is shown for the proteins with multiple spots in 2D-DIGE gels). (B) Volcano plots showing P values (−log10) versus protein ratio of (log2). Red, up-regulated; Green, down-regulated; and Blue, not significantly changed (adjusted p-value > 0.05) proteins. A few selected differentially abundant proteins are labeled. (C) Representative MS/MS spectrum of a few selected differentially abundant proteins. Inset showing the iTRAQ reporter ion intensities for representative peptides in HC, NSVM and SVM. (D) Venn diagram showing the unique and common differentially abundant proteins (p-value ≤ 0.05) in NSVM and SVM identified in iTRAQ analysis by ESI-Q-TOF. (E) Venn diagram showing the unique and overlapping proteins identified in Q-Exactive and ESI-Q-TOF.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835765&req=5

f2: Comparative analysis of serum proteome alterations in NSVM and SVM patients.(A) Trends of a few selected differentially abundant proteins in NSVM and SVM identified in 2D-DIGE. Data are represented as standardized log abundance of spot intensity (One representative spot is shown for the proteins with multiple spots in 2D-DIGE gels). (B) Volcano plots showing P values (−log10) versus protein ratio of (log2). Red, up-regulated; Green, down-regulated; and Blue, not significantly changed (adjusted p-value > 0.05) proteins. A few selected differentially abundant proteins are labeled. (C) Representative MS/MS spectrum of a few selected differentially abundant proteins. Inset showing the iTRAQ reporter ion intensities for representative peptides in HC, NSVM and SVM. (D) Venn diagram showing the unique and common differentially abundant proteins (p-value ≤ 0.05) in NSVM and SVM identified in iTRAQ analysis by ESI-Q-TOF. (E) Venn diagram showing the unique and overlapping proteins identified in Q-Exactive and ESI-Q-TOF.
Mentions: A gel-based proteomics analysis using 2D-DIGE identified approximately 1200 protein spots on each gel in DeCyder 2D software analysis. Comparative serum proteome analysis of HC and SVM revealed differential abundance of 131 protein spots (p < 0.05), among which 75 spots exhibited increased abundance, while the remaining 56 spots were down-regulated (Table S2A). Comparative analysis of NSVM and SVM indicated differential abundance of 26 protein spots, among which 20 were up-regulated and 6 were down-regulated (Table S2B). Identity of 22 protein spots (10 up-regulated and 12 down-regulated) was established by subsequent MALDI-TOF/TOF MS analysis (Table S3). Graphical representations for differential abundance of some selected proteins in NSVM and SVM are shown in Fig. 2A.

Bottom Line: In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure.Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection.Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

ABSTRACT
In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

No MeSH data available.


Related in: MedlinePlus