Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel

Ehsan Kachooei, Ali Akbar Moosavi-Movahedi, Fariba Khodagholi, Faroogh Mozaffarian, Payam Sadeghi, Hamid Hadi-Alijanvand, Atiyeh Ghasemi, Ali Akbar Saboury, Mohammad Farhadi, Nader Sheibani

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Alzheimer, a neurodegenerative disease, and a large variety of pathologic conditions are associated with a form of protein aggregation known as amyloid fibrils. Since fibrils and prefibrillar intermediates are cytotoxic, numerous attempts have been made to inhibit fibrillation process as a therapeutic strategy. Peptides, surfactants and aromatic small molecules have been used as fibrillation inhibitors. Here we studied the effects of paclitaxel, a polyphenol with a high tendency for interaction with proteins, on fibrillation of insulin as a model protein. The effects of paclitaxel on insulin fibrillation were determined by Thioflavin T fluorescence, Congo red absorbance, circular dichroism and atomic force microscopy. These studies indicated that paclitaxel considerably hindered nucleation, and therefore, fibrillation of insulin in a dose-dependant manner. The isothermal titration calorimetry studies showed that the interaction between paclitaxel and insulin was spontaneous. In addition, the van der Waal's interactions and hydrogen bonds were prominent forces contributing to this interaction. Computational results using molecular dynamic simulations and docking studies revealed that paclitaxel diminished the polarity of insulin dimer and electrostatic interactions by increasing the hydrophobicity of its dimer state. Furthermore, paclitaxel reduced disrupting effects of insulin fibrils on PC12 cell's neurite outgrowth and complexity, and enhanced their survival.

LanguageEnglish
Pages361-373
Number of pages13
JournalJournal of Biochemistry
Volume155
Issue number6
DOIs
Publication statusPublished - Jun 2014
Externally publishedYes

Fingerprint

Cytotoxicity
Paclitaxel
Insulin
Neurodegenerative diseases
Congo Red
Calorimetry
Proteins
Atomic Force Microscopy
PC12 Cells
Dichroism
Polyphenols
Molecular Dynamics Simulation
Hydrophobicity
Circular Dichroism
Coulomb interactions
Static Electricity
Titration
Hydrophobic and Hydrophilic Interactions
Amyloid
Surface-Active Agents

Keywords

  • cytotoxicity
  • inhibition
  • insulin fibrillation
  • nucleation
  • paclitaxel

Cite this

Kachooei, E., Moosavi-Movahedi, A. A., Khodagholi, F., Mozaffarian, F., Sadeghi, P., Hadi-Alijanvand, H., ... Sheibani, N. (2014). Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel. Journal of Biochemistry, 155(6), 361-373. https://doi.org/10.1093/jb/mvu012
Kachooei, Ehsan ; Moosavi-Movahedi, Ali Akbar ; Khodagholi, Fariba ; Mozaffarian, Faroogh ; Sadeghi, Payam ; Hadi-Alijanvand, Hamid ; Ghasemi, Atiyeh ; Saboury, Ali Akbar ; Farhadi, Mohammad ; Sheibani, Nader. / Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel. In: Journal of Biochemistry. 2014 ; Vol. 155, No. 6. pp. 361-373.
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Kachooei, E, Moosavi-Movahedi, AA, Khodagholi, F, Mozaffarian, F, Sadeghi, P, Hadi-Alijanvand, H, Ghasemi, A, Saboury, AA, Farhadi, M & Sheibani, N 2014, 'Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel', Journal of Biochemistry, vol. 155, no. 6, pp. 361-373. https://doi.org/10.1093/jb/mvu012

Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel. / Kachooei, Ehsan; Moosavi-Movahedi, Ali Akbar; Khodagholi, Fariba; Mozaffarian, Faroogh; Sadeghi, Payam; Hadi-Alijanvand, Hamid; Ghasemi, Atiyeh; Saboury, Ali Akbar; Farhadi, Mohammad; Sheibani, Nader.

In: Journal of Biochemistry, Vol. 155, No. 6, 06.2014, p. 361-373.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel

AU - Kachooei, Ehsan

AU - Moosavi-Movahedi, Ali Akbar

AU - Khodagholi, Fariba

AU - Mozaffarian, Faroogh

AU - Sadeghi, Payam

AU - Hadi-Alijanvand, Hamid

AU - Ghasemi, Atiyeh

AU - Saboury, Ali Akbar

AU - Farhadi, Mohammad

AU - Sheibani, Nader

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N2 - Alzheimer, a neurodegenerative disease, and a large variety of pathologic conditions are associated with a form of protein aggregation known as amyloid fibrils. Since fibrils and prefibrillar intermediates are cytotoxic, numerous attempts have been made to inhibit fibrillation process as a therapeutic strategy. Peptides, surfactants and aromatic small molecules have been used as fibrillation inhibitors. Here we studied the effects of paclitaxel, a polyphenol with a high tendency for interaction with proteins, on fibrillation of insulin as a model protein. The effects of paclitaxel on insulin fibrillation were determined by Thioflavin T fluorescence, Congo red absorbance, circular dichroism and atomic force microscopy. These studies indicated that paclitaxel considerably hindered nucleation, and therefore, fibrillation of insulin in a dose-dependant manner. The isothermal titration calorimetry studies showed that the interaction between paclitaxel and insulin was spontaneous. In addition, the van der Waal's interactions and hydrogen bonds were prominent forces contributing to this interaction. Computational results using molecular dynamic simulations and docking studies revealed that paclitaxel diminished the polarity of insulin dimer and electrostatic interactions by increasing the hydrophobicity of its dimer state. Furthermore, paclitaxel reduced disrupting effects of insulin fibrils on PC12 cell's neurite outgrowth and complexity, and enhanced their survival.

AB - Alzheimer, a neurodegenerative disease, and a large variety of pathologic conditions are associated with a form of protein aggregation known as amyloid fibrils. Since fibrils and prefibrillar intermediates are cytotoxic, numerous attempts have been made to inhibit fibrillation process as a therapeutic strategy. Peptides, surfactants and aromatic small molecules have been used as fibrillation inhibitors. Here we studied the effects of paclitaxel, a polyphenol with a high tendency for interaction with proteins, on fibrillation of insulin as a model protein. The effects of paclitaxel on insulin fibrillation were determined by Thioflavin T fluorescence, Congo red absorbance, circular dichroism and atomic force microscopy. These studies indicated that paclitaxel considerably hindered nucleation, and therefore, fibrillation of insulin in a dose-dependant manner. The isothermal titration calorimetry studies showed that the interaction between paclitaxel and insulin was spontaneous. In addition, the van der Waal's interactions and hydrogen bonds were prominent forces contributing to this interaction. Computational results using molecular dynamic simulations and docking studies revealed that paclitaxel diminished the polarity of insulin dimer and electrostatic interactions by increasing the hydrophobicity of its dimer state. Furthermore, paclitaxel reduced disrupting effects of insulin fibrils on PC12 cell's neurite outgrowth and complexity, and enhanced their survival.

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U2 - 10.1093/jb/mvu012

DO - 10.1093/jb/mvu012

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SP - 361

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JO - Journal of Biochemistry

T2 - Journal of Biochemistry

JF - Journal of Biochemistry

SN - 0021-924X

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Kachooei E, Moosavi-Movahedi AA, Khodagholi F, Mozaffarian F, Sadeghi P, Hadi-Alijanvand H et al. Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel. Journal of Biochemistry. 2014 Jun;155(6):361-373. https://doi.org/10.1093/jb/mvu012