The influence of phospholipid membranes on bovine calcitonin peptide's secondary structure and induced neurotoxic effects
Resource
The International Journal of Biochemistry & Cell Biology 37(2005), 1656–1669
Journal
The International Journal of Biochemistry & Cell Biology 37(2005), 1656–1669
Pages
-
Date Issued
2005
Date
2005
Author(s)
DOI
246246/2006111501232845
Abstract
The peptide hormone, calcitonin, which is associated with medullary carcinoma of the thyroid, has a marked tendency to form
amyloid fibrils and may be a useful model in probing the role of peptide–membrane interactions in -sheet and amyloid formation
and amyloid neurotoxicity. Using bovine calcitonin, we found that, like other amyloids, the peptide was toxic only when in a -
sheet-rich, amyloid form, butwas non-toxic, when it lacked an amyloid structure.We found that the peptide bound with significant
affinity to membranes that contained either cholesterol and gangliosides. In addition, incubation of calcitonin with cholesterol-rich
and ganglioside-containing membranes resulted in significant changes in peptide structure yielding a peptide enriched in -sheet
and amyloid content. Because the cholesterol- and ganglioside-rich phospholipid systems enhanced the calcitonin -sheet and
amyloid contents, and peptide amyloid contentwas associated with neurotoxicity,we then investigated whether depleting cellular
cholesterol and gangliosides affected calcitonin neurotoxicity. We found that cholesterol and ganglioside removal significantly
reduced the calcitonin-induced PC12 cell neurotoxicity. Similar results have been observed with other amyloid-forming peptides
such as -amyloid (A) of Alzheimer’s disease and suggest that modulation of membrane composition and peptide–membrane
interactions may prove useful in the control of amyloid formation and amyloid neurotoxicity.
Subjects
Calcitonin
Amyloid
Cholesterol
Gangliosides
Secondary structure
Neurotoxicity
Type
journal article
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