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Inhibition of secretory phospholipase A2 enzyme by bilirubin: A new role as endogenous anti-inflammatory molecule

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Abstract

Bilirubin is a powerful antioxidant that suppresses the inflammatory process. However its interaction with proinflammatory PLA2 enzyme is not known. Inhibition of several secretory phospholipase A2 (sPLA2) enzyme activities by bilirubin was studied using 14C-oleate labeled Escherichia coli as substrate. Bilirubin inhibits purified sPLA2 enzyme from Vipera russellii and Naja naja venom and partially purified sPLA2 enzymes from human ascitic fluid, pleural fluid and normal serum in a dose dependent manner. IC50 values calculated for these enzymes ranges from 1.75 to 10.5 μM. Inflammatory human sPLA2 enzymes are more sensitive to inhibition by bilirubin than snake venom sPLA2s. Inhibition of sPLA2 activity by bilirubin is independent of calcium concentration. Increasing substrate concentration (upto 180 nmol) did not relieve the inhibition of sPLA2 by bilirubin and it is irreversible. Bilirubin quenched the relative fluorescence intensity of sPLA2 in a dose dependent manner in the same concentration range at which in vitro sPLA2 inhibition was observed. In the presence of bilirubin, apparent shift in the far UV-CD spectra of sPLA2 was observed, indicating a direct interaction with the enzyme. Inhibition of sPLA2 induced mouse paw edema by bilirubin confirms its sPLA2 inhibitory activity in vivo also. These findings indicate that inhibition of sPLA2 by bilirubin is mediated by direct interaction with the enzyme and bilirubin may act as an endogenous regulator of sPLA2 enzyme activity.

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Authors and Affiliations

  1. Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore, 570 006, India

    Noor Mohamed Jameel, T. Veerabasappa Gowda & Bannikuppe S. Vishwanath

  2. Division of Nephrology, Department of Medicine, University of Bern, 3010, Bern, Switzerland

    Brigitte M. Frey & Felix J. Frey

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  1. Noor Mohamed Jameel
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  2. Brigitte M. Frey
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  3. Felix J. Frey
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  4. T. Veerabasappa Gowda
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  5. Bannikuppe S. Vishwanath
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Correspondence to Noor Mohamed Jameel.

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Jameel, N.M., Frey, B.M., Frey, F.J. et al. Inhibition of secretory phospholipase A2 enzyme by bilirubin: A new role as endogenous anti-inflammatory molecule. Mol Cell Biochem 276, 219–225 (2005). https://doi.org/10.1007/s11010-005-4441-x

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  • DOI: https://doi.org/10.1007/s11010-005-4441-x

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