| Parkinson's disease is the progressive neurodegenerative disease of the central nervous system affecting approximately 1% of the human population aged 65 and above. Parkinsonism is characterized by a combination of rigidity, bradykinesia, tremor, and postural instability that can occur for a wide variety of reasons but is usually idiopathic. Physiologically, PD is characterized by dopamine deficiency owing to the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the midbrain. Its pathological features also include the presence of intracytoplasmic inclusions known as Lewy bodies and decrease of DA. The cause of idiopathic PD remains unknown, and the mechanisms responsible for nigral dopaminergic cell loss are obscure. Oxidative stress, mitochondrial respiration defect and excitotoxicity are three types of cellular dysfunction that play important roles in the pathogenesis of PD. Although major emphasis has been given to the dysfunction of dopaminergic neurons in PD, the activation of glial cells also may play an important role in the initiation and progression of cell death. Indeed, many of the processes which have been suggested to be involved in the pathogenesis of PD including oxidative stress may originate in glial cells. The occurrence of oxidative stress in PD is supported by both postmortem studies and by studies demonstrating the capacity of oxidative stress and oxidizing toxins to induce nigral celldegeneration. There is evidence to support that there are high levels of basal oxidative stress in the substantia nigra pars compacta (SNc) in the normal brain and that this is increased in PD.Astrocytes play an important role in the progressive ofneurodegenerative disease such as PD. Glutathione also is generated inastrocytes. The tripeptide glutathione (GSH; y-L-glutamyl-L-cysteinylglycine) has important functions as antioxidant, is areactionpartner for the detoxication of xenobiotica, is a cofactor in isomerizationreactions, and is a storage and transport form of cysteine. GSH isregulated by a various of enzymes, these enzymes consist of the systemof GSH enzymes. They are (1) y-glutamylcysteine synthetase (yGCS),the rate-limiting enzyme and the first enzyme used in GSH synthesis.(2) The ectoenzyme yGT (y-glutamyl transpeptidase), which convertsGSH to cysteinylglycine (CysGly) and y-glutamyl. (3) Glutathioneperoxidase (GPx) and glutathione reductase (GR), which catalyze theSH/S-S exchange reactions and contribute to protein thiol protection.(4) Glutathione transferases (GST), which use GSH to detoxify peroxidesand carbonyl-containing products of lipid peroxidation.6-OHDA is one of the most common neurotoxins used to model nigral degeneration experimentally in vitro as well as in vivo. 6-OHDA, like dopamine (DA), is a substrate for monoamine oxidase (MAO). And it is usually thought to cross cell membrane through dopamine transporters, to inhibit mitochondrial respiration and to generate intracellular ROS.PART I : Protection of glutathione against 6-OHDA in PC12 cellsAIM: To determine the role of GSH in 6-OHDA treated PC 12 cells. METHORDS: PC 12 cells used in the test of cells viability were divided into six groups: 1) control group; 2) 6-OHDA treated group: 200 uM 6-OHDA; 3) BSO treatment group: BSO 0.05. 0.1. 0.5, 1 mM+6-OHDA 0.2 mM; 4) BSO 1 mM group; 5) NAC treatment group: NAC 0.1. 1. 3 mM NAC+ 0.2 mM 6-OHDA; 6 ) GSH treatment group: 0.1. 0.5. 1 mM GSH + 0.2 mM 6-OHDA. RESULTS: PC12 cells incubated with BSO could enhance the neurotoxicity of 6-OHDA. However, pretreatment with NAC or GSH could relieve the neurotoxicity of 6-OHDA. CONCLUSIONS: These results suggested that GSH could protect PC 12 cells against 6-OHDA.PART II: The role of glutathione and glutathione related enzymes in 6-OHDA treated astrocytesAIM: To investigate the role of 6-OHDA in astrocytes GSH metabolism, and the expression of glutathione-related enzymes, especially yGCS and yGT in primary cultured astrocytes induced by 6-OHDA. METHORDS: (1) Astrocytes used in the test of cell vi... |
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