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Human Amylin Induces “Apoptotic” Pattern of Gene Expression Concomitant with Cortical Neuronal Apoptosis
Author(s) -
Tucker H. Michael,
Rydel Russell E.,
Wright Sarah,
Estus Steven
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71020506.x
Subject(s) - amylin , junb , biology , programmed cell death , apoptosis , gene expression , microbiology and biotechnology , fosb , gene , chromatin , neurodegeneration , genetics , endocrinology , medicine , disease , islet , insulin
Amylin forms large β‐pleated neurotoxic oligomers but shows only 38% sequence similarity to Aβ. As patterns of gene expression during neuronal apoptosis appear stimulus and cell type specific, we compared the pattern of amylin‐induced gene expression in rat cortical neurons with that shown previously to be induced by Aβ in order to evaluate whether these two peptides with different primary but similar secondary structure induce apoptosis similarly. Morphologic and quantitative measures of cell death show widespread apoptotic death after amylin treatment. Amylin treatment results in time‐ and concentration‐dependent inductions of oxidative stress genes, such as cox‐2 and I κ B ‐α. “Apoptotic” genes are also induced in a time‐ and concentration‐dependent manner, including c‐ jun, junB, c‐ fos , and fosB , followed temporally by a gene known to be modulated by these transcription factors, i.e., transin . In situ hybridization analyses show that c‐ fos expression is restricted largely to neurons with condensed chromatin, a hallmark of apoptosis. As these genes are not induced in all models of apoptosis, that amylin‐induced neuronal death is genetically similar to that of Aβ suggests that these peptides may be neurotoxic through a common mechanism.