01 November 2005
Substitution of methionine 35 inhibits apoptotic effects of Abeta(31-35) and Abeta(25-35) fragments of amyloid-beta protein in PC12 cells.
Maria Elisabetta Clementi, Francesco MisitiMed Sci Monit 2005; 11(11): BR381-385 :: ID: 430276
Abstract
BACKGROUND: Amyloid-beta peptide (AbetaP), the central constituent of senile plaques in Alzheimer's disease (AD) brain, has been shown to be toxic to neuronal cells and that this toxicity is responsible for the progressive cognitive decline associated with this neurodegenerative disease. The precise mechanism of AbetaP action remains to be determined; however, it has been reported that the methionine residue at position 35 plays a pivotal role in the toxicity of the peptide. With this in mind, the present study examines the effect of mutating the methionine to norleucine in the fragments (31-35) and (25-35) of AbetaP, which have methionine at the C-terminal, in order to investigate the influence of this residue on Abeta-mediated toxic effects on PC12 cells. MATERIAL/METHODS: The toxic and apoptotic effects (release of Cyt c, caspase activation, and DNA fragmentation) exerted by the Abeta(31-35) and Abeta(25-35) wild-type peptides and Abeta(31-35)Met-->Nle, Abeta(25-35)Met-->Nle peptides where methionine was substituted with norleucine were investigated on PC12 cells. RESULTS: The results obtained shown that both peptides induce neurotoxicity in PC12 cells via an apoptotic cell death pathway, including cytochrome c release, caspase activation, and DNA fragmentation. Furthermore, this study reveals that these events were completely abrogated in cells exposed to Abeta peptides in which methionine 35 was substituted by a norleucine residue. CONCLUSIONS: On the basis of the results obtained in this study, an additional hypothesis involving the amyloid-beta peptide and the role of Met-35 has been proposed to clarify the mechanisms responsible of neurodegeneration in Alzheimer's disease.
Keywords: Amyloid beta-Peptides - toxicity, Amino Acid Substitution - genetics, Caspases - analysis, Cytochromes c - analysis, Methionine - genetics, Neurons - enzymology, Norleucine - genetics, Peptide Fragments - toxicity
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
21 Mar 2024 : Meta-Analysis
Economic Evaluation of COVID-19 Screening Tests and Surveillance Strategies in Low-Income, Middle-Income, a...Med Sci Monit In Press; DOI: 10.12659/MSM.943863
10 Apr 2024 : Clinical Research
Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Dep...Med Sci Monit In Press; DOI: 10.12659/MSM.942612
06 Mar 2024 : Clinical Research
Enhanced Surgical Outcomes of Popliteal Cyst Excision: A Retrospective Study Comparing Arthroscopic Debride...Med Sci Monit In Press; DOI: 10.12659/MSM.941102
06 Mar 2024 : Clinical Research
Prevalence and Variation of Medical Comorbidities in Oral Surgery Patients: A Retrospective Study at Jazan ...Med Sci Monit In Press; DOI: 10.12659/MSM.943884
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952