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 Misiti
Med Sci Monit 2005; 11(11): BR381-385 :: ID: 430276
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, PC12 Cells, Peptide Fragments - toxicity
01 May 2022 : EditorialEditorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19
Med Sci Monit 2022; 28:e937048
04 May 2022 : Clinical ResearchEffects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936069
27 May 2022 : Clinical ResearchFactors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)
Med Sci Monit 2022; 28:e936547
27 May 2022 : Clinical ResearchPrognostic Significance of Preoperative Integrated Liver Inflammatory Score in Patients with Hepatocellular...
Med Sci Monit In Press; DOI: 10.12659/MSM.937005
25 May 2022 : Review articleNarrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of Dislocation
Med Sci Monit In Press; DOI: 10.12659/MSM.935665
24 May 2022 : Clinical ResearchRemimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936580
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
01 Nov 2020 : Review articleLong-Term Respiratory and Neurological Sequelae of COVID-19
Med Sci Monit 2020; 26:e928996