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Guanidination of notexin alters its membrane-damaging activity in response to sphingomyelin and cholesterol

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Abstract

To elucidate the contribution of phospholipase A2 (PLA2) activity of notexin to its ability to perturb membranes, comparative studies on the interaction of notexin and guanidinated notexin (Gu-notexin) with egg yolk phosphatidylcholine (EYPC), EYPC/egg yolk sphingomyelin (EYSM) and EYPC/EYSM/cholesterol vesicles were conducted. EYSM notably reduced the membrane-damaging activity of notexin against EYPC vesicles, but had an insignificant influence on that of Gu-notexin. Unlike the effects noted with notexin, inactivation of PLA2 activity by EDTA led to a reduction in the ability of Gu-notexin to induce EYPC/EYSM vesicle leakage and to increase Gu-notexin-induced membrane permeability of EYPC/EYSM/cholesterol vesicles. The geometrical arrangement of notexin and Gu-notexin in contact with either EYPC/EYSM vesicles or EYPC/EYSM/cholesterol vesicles differed. Moreover, global conformation of notexin and Gu-notexin differed in either Ca2+-bound or metal-free states. These results indicate that notexin and Gu-notexin could induce membrane permeability without the involvement of PLA2 activity, and suggest that guanidination alters the membrane-bound mode of notexin on damaging phospholipid vesicles containing sphingomyelin and cholesterol.

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Abbreviations

CD:

circular dichroism

EYPC:

egg yolk phosphatidylcholine

EYSM:

egg yolk sphingomyelin

FTIR:

Fourier transform infrared

PLA2 :

phospholipase A2

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Authors and Affiliations

  1. Institute of Biomedical Sciences, National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

    Pei-Hsiu Kao, Yi-Ling Chiou & Long-Sen Chang

  2. Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Shinne-Ren Lin

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  1. Pei-Hsiu Kao
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  2. Yi-Ling Chiou
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  3. Shinne-Ren Lin
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  4. Long-Sen Chang
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Correspondence to Long-Sen Chang.

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Kao, PH., Chiou, YL., Lin, SR. et al. Guanidination of notexin alters its membrane-damaging activity in response to sphingomyelin and cholesterol. J Biosci 35, 583–593 (2010). https://doi.org/10.1007/s12038-010-0067-6

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  • DOI: https://doi.org/10.1007/s12038-010-0067-6

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