Structure‐activity relationship of heme and its analogues in membrane damage and inhibition of fusion

Under pathological conditions, such as sickle cell disease and malaria, heme concentration increases considerably, and it induces membrane damage. As sickled and normal erythrocytes contain high cholesterol: phospholipid ratio, we investigated the role of lipid composition, chain length, and unsatur...

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Bibliographic Details
Published in:FEBS letters 2018-07, Vol.592 (14), p.2458-2465
Main Authors: Das, Debashree, Tarafdar, Pradip K., Chakrabarti, Abhijit
Format: Article
Language:English
Subjects:
cholesterol
membrane fusion
membrane partitioning
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Summary:Under pathological conditions, such as sickle cell disease and malaria, heme concentration increases considerably, and it induces membrane damage. As sickled and normal erythrocytes contain high cholesterol: phospholipid ratio, we investigated the role of lipid composition, chain length, and unsaturation on the partitioning and leakage of hemin in phospholipid vesicles. To establish structure‐activity relationship in membrane damage, experiments with two other analogues, protoporphyrin‐IX and hematoporphyrin (HP) were also carried out. Hemin and its analogues localize differently in membranes and exhibit distinct roles in partitioning, leakage and fusion. Hemin and HP trigger more leakage in the presence of aminophospholipids, whereas cholesterol buffers the destabilizing effect remarkably. Inhibition of fusion by hemin further suggests its unexplored and important role in membrane trafficking, particularly under diseased conditions.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.13165