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PC12 is a cell line derived from a pheochromocytoma of the rat adrenal medulla, that have an embryonic origin from the neural crest that has a mixture of neuroblastic cells and eosinophilic cells.
Contents
- Background
- Differentiation
- Nerve Growth Factor
- Dexamethasone
- Drugs effects on vesicles
- Research
- References
Background
This cell line was first cultured by Greene and Tischler in 1976. It was developed in parallel to the adrenal chromaffin cell model because of its extreme versatility for pharmacological manipulation, ease of culture, and the large amount of information on their proliferation and differentiation. These qualities provide advantage even though they have smaller vesicles and quantal size, holding only an average of 1.9x10−19 moles of neurotransmitter released. The vesicles hold catecholamines, mostly dopamine but also limited amount of norepinephrine, and release of these neurotransmitters give rise to spikes due to changes in current similar to chromaffin cells.
PC12 cell line use has given much information to the function of proteins underlying vesicle fusion. Used to understand the role of synaptotagmin in vesicle fusion, in which increase in calcium concentration displaces synaptotagmin and catalyzes membrane fusion.
Differentiation
Their embryological origin with neuroblastic cells means they can easily differentiate into neuron-like cells even though they are not considered adult neurons. Neuron-like means they share properties similar to neurons, in this case it is referring to releasing neurotransmitter by vesicles. PC12 cells stop dividing and terminally differentiate when treated with nerve growth factor or dexamethasone. This makes PC12 cells useful as a model system for neuronal differentiation and neurosecretion.
Nerve Growth Factor
Treatment of PC12 cells with nerve growth factor creates cells with long processes known as neurite varicosities, which contain small amounts of vesicles. PC12 cells treated for 10–14 days with nerve growth factor had no release of vesicles from the cell body which indicates the aggregation of vesicles in the ends of the neurites.
Dexamethasone
Treatment of PC12 cells with dexamethasone differentiates them into chromaffin-like cells. Using patch clamp recording and amperometry there was a significant increase in quantal size, excitability and coupling between calcium channels and vesicle release sites, increasing from ~2x10−19 to ~6.5x10−19 moles.
Drugs effects on vesicles
Research has shown differences in vesicle size and quantal size depending on treatment with certain drugs.
Research
The PC12 cell line has been used to get more information about diseases of the brain. It has been used in research of hypoxia, where acute hypoxia induces exocytosis and prolonged hypoxia can induce excessive exocytosis. PC12 cells were used to find which prion protein fragments caused neuronal dysfunction. PC12 was used partly for some forms of Parkinson's disease with finds that support interference after vesicle docking and prior to vesicle release.