Effects of tocopherols and 2,2′-carboxyethyl hydroxychromans on phorbol-ester-stimulated neutrophils

Z. Varga, Eszter Kosaras, Edina Komodi, Monika Katko, Istvan Karpati, J. Balla, G. Paragh, Maria C. Aisa, Francesco Galli

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Tocopherol vitamers [e.g., alpha-, gamma- and delta-tocopherol (α-TOC, γ-TOC and δ-TOC, respectively)] and their water-soluble 2,2′-carboxyethyl hydroxychroman metabolites (e.g., α-, γ- and δ-CEHC) all possess antioxidant properties. As a consequence, and similarly to other natural antioxidants, vitamin E compounds may be useful in preventing inflammatory and oxidative-stress-mediated diseases. In this study, we investigated the concentration-dependent effect of tocopherols and water-soluble metabolites on a key event in oxidative stress, for example, the oxidative burst in neutrophils. It was found that not only α-TOC but also γ-TOC and δ-TOC as well as α-, γ- and δ-CEHC at physiological concentrations inhibit superoxide anion (O2 •-) production in phorbol-ester-stimulated neutrophils. This effect was mediated by the inhibition of the translocation and activation of protein kinase C (PKC) enzyme, which is the key event in the phorbol-ester signaling. Importantly, CEHCs were stronger inhibitors of PKC as compared with the vitamer precursors, and the gamma forms of both tocopherol and CEHC showed the highest inhibitory activities. Tocopherols, but not CEHCs, directly inhibit the fully activated nicotine-adenine-dinucleotide phosphate (NADPH) oxidase. However, none of the test compounds was able to directly scavenge O2 •- when tested in a cell-free system. In conclusion, vitamin E compounds can control the neutrophil oxidative burst through the negative modulation of PKC-related signaling and NADPH oxidase activity. As an original finding, we observed that CEHC metabolites might contribute to regulate PKC activity in these cells. These results may have important implications in the anti-inflammatory and antioxidant role of vitamin E compounds.

Original languageEnglish
Pages (from-to)320-327
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume19
Issue number5
DOIs
Publication statusPublished - May 2008

Fingerprint

Tocopherols
Phorbol Esters
Protein Kinase C
Neutrophils
Metabolites
Vitamin E
Oxidative stress
Respiratory Burst
Antioxidants
Adenine
Nicotine
Oxidoreductases
Oxidative Stress
Phosphates
gamma-Tocopherol
Cell-Free System
Water
alpha-Tocopherol
Superoxides
Anti-Inflammatory Agents

Keywords

  • CEHC
  • NADPH oxidase
  • Neutrophils
  • Protein kinase C
  • Tocopherols
  • Vitamin E
  • Xanthine oxidase

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of tocopherols and 2,2′-carboxyethyl hydroxychromans on phorbol-ester-stimulated neutrophils. / Varga, Z.; Kosaras, Eszter; Komodi, Edina; Katko, Monika; Karpati, Istvan; Balla, J.; Paragh, G.; Aisa, Maria C.; Galli, Francesco.

In: Journal of Nutritional Biochemistry, Vol. 19, No. 5, 05.2008, p. 320-327.

Research output: Contribution to journalArticle

Varga, Z. ; Kosaras, Eszter ; Komodi, Edina ; Katko, Monika ; Karpati, Istvan ; Balla, J. ; Paragh, G. ; Aisa, Maria C. ; Galli, Francesco. / Effects of tocopherols and 2,2′-carboxyethyl hydroxychromans on phorbol-ester-stimulated neutrophils. In: Journal of Nutritional Biochemistry. 2008 ; Vol. 19, No. 5. pp. 320-327.
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AU - Kosaras, Eszter

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AU - Katko, Monika

AU - Karpati, Istvan

AU - Balla, J.

AU - Paragh, G.

AU - Aisa, Maria C.

AU - Galli, Francesco

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