Antagonistic effects of ultra-low-molecular-weight heparin on Aβ25-35-induced apoptosis in cultured rat cortical neurons.
Low-molecular-weight heparin (LMWH) and ultra-low-molecular-weight heparin (ULMWH) are heparin's derivatives, having various pharmacological effects. The present study aims to investigate the effect of ULMWH on amyloid β peptide (Aβ25-35)-induced neurotoxicity in cultured rat cortical neurons, and LMWH was employed as a positive control agent. The neurons were incubated with Aβ25-35 (35μM), Aβ25-35 plus ULMWH (2, 10, 50 μg/ml) or LMWH (10 μg/ml) for 24h. The cell viability was assessed by MTT and LDH release. FITC-Annexin V/PI double staining, Hoechst 33258 staining, TUNEL and Western blotting for bcl-2 and caspase-3 were employed to measure the neuron apoptosis. Furthermore, the intracellular Ca(2+) concentration was measured by a fluorescent dye, Fura-2/AM. The results showed that ULMWH significantly increased cell viability and the protein expression levels of bcl-2 and decreased the LDH release, the number of apoptotic cells, the concentration of intracellular Ca(2+) and the protein expression levels of caspase-3 in cortical neurons, suggesting that ULMWH can obviously reduce Aβ25-35-induced neurotoxic effects and might act as a potential agent for Alzheimer's disease.
Hao
Li-na
LN
Pharmacological Institute of New Drugs, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, P.R. China.
Zhang
Qing-zhu
QZ
Yu
Tian-gui
TG
Cheng
Yan-na
YN
Ji
Sheng-li
SL
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D002118:Calcium