Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability through formation of "off-pathway" oligomers

Ehsan Kachooei, Faroogh Mozaffarian, Fariba Khodagholi, Payam Sadeghi, Leila Karami, Atiyeh Ghasemi, Elham Vahdat, Ali Akbar Saboury, Nader Sheibani, Ali Akbar Moosavi-Movahedi

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Protein fibrillation is a challenging issue in medicine, causing many diseases, and an impediment to pharmaceutics and protein industry. Many chemicals, especially polyphenol compounds and aromatic small molecules, have been widely used as an effective strategy to combat protein fibril formation. Hence, understanding mechanisms of fibrillation inhibition and contributing forces in this process are significant. In this study, the inhibitory effect of paclitaxel on lysozyme fibrillation was investigated with respect to thermal and colloidal stability. Fibrillation was monitored with ThT fluorescence, circular dichroism, and AFM; paclitaxel-lysozyme interaction with isothermal titration calorimetry and docking; thermal and colloidal stability with differential scanning calorimetry and zeta-pulse, respectively. Paclitaxel inhibited lysozyme fibrillation, and interacted with lysozyme through hydrogen bonds and van der Waals' interactions. The viability of PC12 cells retrieved as a result of fibrillation inhibition by paclitaxel. Hydrophobic forces dominantly shielded the aggregation-prone region of lysozyme and suppressed the effective interactions between lysozyme monomers. Although paclitaxel did not affect lysozyme's thermal stability, it increased lysozyme's colloidal stability by either increasing the surface charge density or charge distribution on lysozyme. In conclusion, our results suggest a model for paclitaxel's inhibitory role through two complementary steps driving to "off-pathway" oligomer formation and attenuation of fibril formation.

LanguageEnglish
Pages870-879
Number of pages10
JournalInternational Journal of Biological Macromolecules
Volume111
DOIs
Publication statusPublished - May 2018
Externally publishedYes

Fingerprint

Muramidase
Paclitaxel
Oligomers
Enzymes
Hot Temperature
Proteins
Fibrillation
Pathway
Calorimetry
PC12 Cells
Charge distribution
Differential Scanning Calorimetry
Drug Industry
Dichroism
Polyphenols
Surface charge
Circular Dichroism
Charge density
Titration
Medicine

Keywords

  • Amyloid
  • Polyphenol
  • Calorimetry
  • Thermal stability
  • Zeta potential

Cite this

Kachooei, Ehsan ; Mozaffarian, Faroogh ; Khodagholi, Fariba ; Sadeghi, Payam ; Karami, Leila ; Ghasemi, Atiyeh ; Vahdat, Elham ; Saboury, Ali Akbar ; Sheibani, Nader ; Moosavi-Movahedi, Ali Akbar. / Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability through formation of "off-pathway" oligomers. In: International Journal of Biological Macromolecules. 2018 ; Vol. 111. pp. 870-879.
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abstract = "Protein fibrillation is a challenging issue in medicine, causing many diseases, and an impediment to pharmaceutics and protein industry. Many chemicals, especially polyphenol compounds and aromatic small molecules, have been widely used as an effective strategy to combat protein fibril formation. Hence, understanding mechanisms of fibrillation inhibition and contributing forces in this process are significant. In this study, the inhibitory effect of paclitaxel on lysozyme fibrillation was investigated with respect to thermal and colloidal stability. Fibrillation was monitored with ThT fluorescence, circular dichroism, and AFM; paclitaxel-lysozyme interaction with isothermal titration calorimetry and docking; thermal and colloidal stability with differential scanning calorimetry and zeta-pulse, respectively. Paclitaxel inhibited lysozyme fibrillation, and interacted with lysozyme through hydrogen bonds and van der Waals' interactions. The viability of PC12 cells retrieved as a result of fibrillation inhibition by paclitaxel. Hydrophobic forces dominantly shielded the aggregation-prone region of lysozyme and suppressed the effective interactions between lysozyme monomers. Although paclitaxel did not affect lysozyme's thermal stability, it increased lysozyme's colloidal stability by either increasing the surface charge density or charge distribution on lysozyme. In conclusion, our results suggest a model for paclitaxel's inhibitory role through two complementary steps driving to {"}off-pathway{"} oligomer formation and attenuation of fibril formation.",
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author = "Ehsan Kachooei and Faroogh Mozaffarian and Fariba Khodagholi and Payam Sadeghi and Leila Karami and Atiyeh Ghasemi and Elham Vahdat and Saboury, {Ali Akbar} and Nader Sheibani and Moosavi-Movahedi, {Ali Akbar}",
year = "2018",
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Kachooei, E, Mozaffarian, F, Khodagholi, F, Sadeghi, P, Karami, L, Ghasemi, A, Vahdat, E, Saboury, AA, Sheibani, N & Moosavi-Movahedi, AA 2018, 'Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability through formation of "off-pathway" oligomers', International Journal of Biological Macromolecules, vol. 111, pp. 870-879. https://doi.org/10.1016/j.ijbiomac.2018.01.072

Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability through formation of "off-pathway" oligomers. / Kachooei, Ehsan; Mozaffarian, Faroogh; Khodagholi, Fariba; Sadeghi, Payam; Karami, Leila; Ghasemi, Atiyeh; Vahdat, Elham; Saboury, Ali Akbar; Sheibani, Nader; Moosavi-Movahedi, Ali Akbar.

In: International Journal of Biological Macromolecules, Vol. 111, 05.2018, p. 870-879.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability through formation of "off-pathway" oligomers

AU - Kachooei, Ehsan

AU - Mozaffarian, Faroogh

AU - Khodagholi, Fariba

AU - Sadeghi, Payam

AU - Karami, Leila

AU - Ghasemi, Atiyeh

AU - Vahdat, Elham

AU - Saboury, Ali Akbar

AU - Sheibani, Nader

AU - Moosavi-Movahedi, Ali Akbar

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N2 - Protein fibrillation is a challenging issue in medicine, causing many diseases, and an impediment to pharmaceutics and protein industry. Many chemicals, especially polyphenol compounds and aromatic small molecules, have been widely used as an effective strategy to combat protein fibril formation. Hence, understanding mechanisms of fibrillation inhibition and contributing forces in this process are significant. In this study, the inhibitory effect of paclitaxel on lysozyme fibrillation was investigated with respect to thermal and colloidal stability. Fibrillation was monitored with ThT fluorescence, circular dichroism, and AFM; paclitaxel-lysozyme interaction with isothermal titration calorimetry and docking; thermal and colloidal stability with differential scanning calorimetry and zeta-pulse, respectively. Paclitaxel inhibited lysozyme fibrillation, and interacted with lysozyme through hydrogen bonds and van der Waals' interactions. The viability of PC12 cells retrieved as a result of fibrillation inhibition by paclitaxel. Hydrophobic forces dominantly shielded the aggregation-prone region of lysozyme and suppressed the effective interactions between lysozyme monomers. Although paclitaxel did not affect lysozyme's thermal stability, it increased lysozyme's colloidal stability by either increasing the surface charge density or charge distribution on lysozyme. In conclusion, our results suggest a model for paclitaxel's inhibitory role through two complementary steps driving to "off-pathway" oligomer formation and attenuation of fibril formation.

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KW - Amyloid

KW - Polyphenol

KW - Calorimetry

KW - Thermal stability

KW - Zeta potential

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