View source for PC12 cell line

[[File:Pc12may28-MAY-28-2011.19.26.39-4.jpg|thumb|PC 12 cells, having been cultured about two days.]]
'''PC12''' is a [[Cell culture#Common cell lines|cell line]] derived from a [[pheochromocytoma]] of the [[rat]] [[adrenal medulla]], that have an [[Embryonic stem cell|embryonic]] origin from the [[neural crest]] that has a mixture of [[neuroblast|neuroblastic cells]] and [[eosinophilic|eosinophilic cells]].<ref name=pmid1065897>{{cite journal |last1=Greene |first1=L A |last2=Tischler |first2=A S |title=Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor |journal=Proceedings of the National Academy of Sciences of the United States of America |date=July 1976 |volume=73 |issue=7 |pages=2424–2428 |doi=10.1073/pnas.73.7.2424 |pmid=1065897 |pmc=430592 |bibcode=1976PNAS...73.2424G |doi-access=free }}</ref><ref name="urlLGC Promochem: Cell Biology Collection">{{cite web | url = http://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=CRL-1721&Template=cellBiology | title = PC-12/CRL-1721 cell line | work = LGC Promochem: Cell Biology Collection | publisher = [[American Type Culture Collection]] | accessdate = 2008-08-15 | url-status = dead | archiveurl = https://web.archive.org/web/20110411150838/http://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=CRL-1721&Template=cellBiology | archivedate = 2011-04-11 }}</ref><ref name=NodarPathology2013>{{cite web | url = http://www.pathologyoutlines.com/topic/adrenalembryology.html | title = Adrenal Gland and Paraganglia - Embryology}}</ref>
==Background==
This cell line was first cultured by Greene and Tischler in 1976.<ref name=pmid1065897/> 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.<ref name="PC12 Neurosecretion">{{cite journal |last1=Westerink |first1=R. H. S. |author2-link=Andrew G. Ewing |last2=Ewing |first2=A. G. |title=The PC12 cell as model for neurosecretion: PC12 cells as model for neurosecretion |journal=Acta Physiologica |date=15 November 2007 |volume=192 |issue=2 |pages=273–285 |doi=10.1111/j.1748-1716.2007.01805.x |pmid=18005394 |pmc=2663028 }}</ref>  These qualities provide advantage even though they have smaller [[vesicle (biology and chemistry)|vesicles]] and quantal size, holding only an average of 1.9x10<sup>−19</sup> moles of neurotransmitter released.<ref name="PC12 Neurosecretion"/>  The vesicles hold [[catecholamine]]s, 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]].  This cell line has been used to understand the role of [[synaptotagmin 1|synaptotagmin]] in vesicle-cell membrane fusion.<ref>{{cite journal |last1=Gustavsson |first1=Natalia |last2=Han |first2=Weiping |title=Calcium-sensing beyond neurotransmitters: functions of synaptotagmins in neuroendocrine and endocrine secretion |journal=Bioscience Reports |date=1 August 2009 |volume=29 |issue=4 |pages=245–259 |doi=10.1042/BSR20090031 |pmid=19500075 |s2cid=29496725 |s2cid-access=free }}</ref>
==Differentiation==
Their [[embryology|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 [[Cellular differentiation|differentiate]] when treated with [[nerve growth factor]] or [[dexamethasone]].<ref>[http://cancerweb.ncl.ac.uk/cgi-bin/omd?pc12+cells Center for Cancer Education]</ref> 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.<ref name="PC12 Neurosecretion"/>
===Dexamethasone===
Treatment of PC12 cells with dexamethasone differentiates them into chromaffin-like cells.   Using [[Patch clamp|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<sup>−19</sup> to ~6.5x10<sup>−19</sup> moles.<ref name="PC12 Neurosecretion"/>
==Drugs effects on vesicles==
Research has shown differences in vesicle size and quantal size depending on treatment with certain drugs.
* [[L-DOPA]] has shown increase in average quantal size when treated for only 40–90 minutes.<ref name="PC12 Neurosecretion"/>
* Treatment with [[amphetamine]] or [[reserpine]] causes a reduction in vesicle content.<ref name="PC12 Neurosecretion"/>
* Inserting the [[heavy metal (chemistry)|heavy metals]] Lead(II), Cadmium(II), Strontium(II), or Barium(II) have been shown to have agonist to the calcium-sensor synaptotagmin.<ref name="PC12 Neurosecretion"/>
* Other [[organic compound|organics]] have been studied using this cell line to understand their effects on PC12 cells   These types of studies show that use of PC12 cell line can be a model for past and future neurotoxicological studies.<ref>{{cite journal |last1=Lankri |first1=David |last2=Haham |first2=Dikla |last3=Lahiani |first3=Adi |last4=Lazarovici |first4=Philip |last5=Tsvelikhovsky |first5=Dmitry |title=Methylene-Cycloalkylacetate (MCA) Scaffold-Based Compounds as Novel Neurotropic Agents |journal=ACS Chemical Neuroscience |date=18 April 2018 |volume=9 |issue=4 |pages=691–698 |doi=10.1021/acschemneuro.7b00473 |pmid=29265805 }}</ref>
== Drugs effects on dopamine metabolism ==
PC12 cells have been researched to evaluate the potential for pharmaceutical alternation of dopamine metabolites such as [[3,4-Dihydroxyphenylacetaldehyde|DOPAL]], an autotoxin implicated in the pathology of [[Parkinson's disease]].<ref>{{Cite journal |last1=Masato |first1=Anna |last2=Plotegher |first2=Nicoletta |last3=Boassa |first3=Daniela |last4=Bubacco |first4=Luigi |date=2019-08-20 |title=Impaired dopamine metabolism in Parkinson's disease pathogenesis |journal=Molecular Neurodegeneration |volume=14 |issue=1 |pages=35 |doi=10.1186/s13024-019-0332-6 |issn=1750-1326 |pmc=6728988 |pmid=31488222 |doi-access=free }}</ref>
* MAO-B inhibitors [[rasagiline]] and [[selegiline]] decreased DOPAL formation.<ref name=":0">{{Cite journal |last1=Goldstein |first1=David S. |last2=Jinsmaa |first2=Yunden |last3=Sullivan |first3=Patti |last4=Holmes |first4=Courtney |last5=Kopin |first5=Irwin J. |last6=Sharabi |first6=Yehonatan |date=February 2016 |title=Comparison of Monoamine Oxidase Inhibitors in Decreasing Production of the Autotoxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde in PC12 Cells |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=356 |issue=2 |pages=483–492 |doi=10.1124/jpet.115.230201 |issn=1521-0103 |pmc=4746494 |pmid=26574516}}</ref>
* Most reversible MAO-A inhibitors failed to decrease DOPAL formation, however the irreversible MAO-A inhibitor [[Clorgiline|clorgyline]] decreased DOPAL production.<ref name=":0" />
==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 (medical)|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.<ref name="PC12 Neurosecretion"/>
In addition to the monoamine (dopamine and norepinephrine) pathway, PC12 cells have been reported to express both the kynurenine and serotonin pathways. Support for this assertion includes both RT-PCR evidence for expression of the required enzymes and changes in expression upon treatment with melatonin.<ref>{{cite journal |last1=Li |first1=Yang |last2=Hu |first2=Nan |last3=Yang |first3=Dan |last4=Oxenkrug |first4=Gregory |last5=Yang |first5=Qing |title=Regulating the balance between the kynurenine and serotonin pathways of tryptophan metabolism |journal=The FEBS Journal |date=March 2017 |volume=284 |issue=6 |pages=948–966 |doi=10.1111/febs.14026 |pmid=28118532 |s2cid=5534560 |doi-access=free }}</ref> A contrary view regarding expression of the serotonin pathway by PC12 cells was expressed by the investigators who first established this cell line.<ref name=pmid1065897/>
== See also ==
* [[Cell culture]]
* [[Adrenal medulla]]
* [[Cellular differentiation]]
* [[Pheochromocytoma]]
== References ==
{{Reflist}}
== External links ==
* Wikipedia articles containing the term "PC12 cells" [https://www.google.com/search?hl=en&lr=&ie=ISO-8859-1&q=site%3Aen.wikipedia.org%20PC12%20cells&btnG=Google+Search]
* Ras function was partially elucidated using PC12 cell line [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=PC12&rid=cmed6.section.1080%231085&WebEnv=0HOhQ10ImJdCL8QWhv8jmakihA5e0QxWqJ9y9n6jvarcLiUb7GMU98BOrUDQVrkDGg5Ona-7T5nkW-%40D45D6EC76612AEB0_0018SID&WebEnvRq=1], from section in Cancer Medicine textbook
* Section on neural transmission [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=PC12&rid=bnchm.section.688#697] has several references to PC12 cell line
*[https://www.cellosaurus.org/CVCL_0481 Cellosaurus entry for PC12]
[[Category:Rodent cell lines]]