β-amyloid (25-35) enhances lipid metabolism and protein ubiquitination in cultured neurons

Emanuela Cazzaniga, Alessandra Bulbarelli, Arianna Cassetti, Elena Lonati, Francesca Re, Paola Palestini, Tatsuro Mutoh, Massimo Masserini

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Abstract

We investigated the effect of β-amyloid (Aβ) (25-35), a cytotoxic fragment of Aβ peptide, on lipid metabolism and protein ubiquitination in cultured rat hippocampal neurons. After treatment with Aβ under conditions leading to apoptotis, as assessed by caspase activity assay, the total cell mass of lipids changed following a biphasic behavior, with an increase that reached a maximum after 16 hr of treatment, followed by a decrease. The increase at 16 hr was 15.3% in the case of phospholipids and 103.0% in the case of gangliosides and was due to enhanced biosynthesis as confirmed by increase of radioactivity incorporation (phospholipids +52.0%, gangliosides +193.1%) in cells fed with tritiated palmitic acid. No change with respect to cholesterol was observed. Strikingly, under these conditions, the ubiquitination state of cell proteins strongly increased. These effects were not observed with the (35-25) reverse sequence peptide. Similarly to Aβ, lactacystin treatment increased lipid synthesis and protein ubiquitination; only lactacystin, and not Aβ, induced a strong decrease of proteasome chimotrypsin activity. These results suggest that Aβ enhances protein ubiquitination, without inhibiting proteasomal activity, and lipid synthesis. These results may shed new light on the mechanisms of Aβ toxicity.

Original languageEnglish
Pages (from-to)2253-2261
Number of pages9
JournalJournal of Neuroscience Research
Volume85
Issue number10
DOIs
Publication statusPublished - 01-08-2007

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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    Cazzaniga, E., Bulbarelli, A., Cassetti, A., Lonati, E., Re, F., Palestini, P., Mutoh, T., & Masserini, M. (2007). β-amyloid (25-35) enhances lipid metabolism and protein ubiquitination in cultured neurons. Journal of Neuroscience Research, 85(10), 2253-2261. https://doi.org/10.1002/jnr.21354