Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis.
Methamphetamine (METH) is an abused drug that may cause psychiatric and neurotoxic damage, including degeneration of monoaminergic terminals and apoptosis of non-monoaminergic cells in the brain. The cellular and molecular mechanisms underlying these METH-induced neurotoxic effects remain to be clarified. In this study, we performed a time course assessment to investigate the effects of METH on intracellular oxidative stress and mitochondrial alterations in a human dopaminergic neuroblastoma SH-SY5Y cell line. We characterized that METH induces a temporal sequence of several cellular events including, firstly, a decrease in mitochondrial membrane potential within 1 h of the METH treatment, secondly, an extensive decline in mitochondrial membrane potential and increase in the level of reactive oxygen species (ROS) after 8 h of the treatment, thirdly, an increase in mitochondrial mass after the drug treatment for 24 h, and finally, a decrease in mtDNA copy number and mitochondrial proteins per mitochondrion as well as the occurrence of apoptosis after 48 h of the treatment. Importantly, vitamin E attenuated the METH-induced increases in intracellular ROS level and mitochondrial mass, and prevented METH-induced cell death. Our observations suggest that enhanced oxidative stress and aberrant mitochondrial biogenesis may play critical roles in METH-induced neurotoxic effects.
Wu
Chi-Wei
CW
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112, ROC.
Ping
Yueh-Hsin
YH
Yen
Jiin-Cherng
JC
Chang
Chia-Yu
CY
Wang
Sheng-Fan
SF
Yeh
Chiao-Ling
CL
Chi
Chin-Wen
CW
Lee
Hsin-Chen
HC
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000697:Central Nervous System Stimulants / Q000633:toxicity; D003513:Cycloheximide / Q000494:pharmacology; D004272:DNA, Mitochondrial / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005452:Fluoresceins / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D018628:Gene Dosage; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008694:Methamphetamine / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D053142:Mitochondrial Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D000697:Central Nervous System Stimulants; D004272:DNA, Mitochondrial; D005452:Fluoresceins; D024101:Mitochondrial Proteins; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; D014810:Vitamin E; C029569:diacetyldichlorofluorescein; D008694:Methamphetamine; D003513:Cycloheximide