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Astrocyte proteins and morphine addiction
up-regulated proteins included cytoskeletal proteins, chaperones, and proteins involved in biosynthesis. Sabine Spijker Although morphine has a long hisof VU University Amsterdam says that tory as a narcotic pain killer, little is despite the use of this culture system, known about how the drug functions several of these proteins also have been at the molecular level. How does the found to be differentially regulated in in drug relieve pain? Why is it so addicvivo studies of the effects of morphine tive? To begin to address some of these and other addictive drugs. “The results questions, Piotr Suder and co-workers could indicate that a lot of the changes at Jagiellonian University, Silesian Uniwe see that we treat as being neuversity, the Medical University of ronal may be of glial origin,” she Lublin (all in Poland), and the points out. Medical University of Vienna have Notably absent from the list of analyzed the proteomes of whole regulated proteins are proinflammabrains and neurons exposed to tory cytokines, such as interleukins. morphine. Now, they report in (Other researchers have reported JPR (DOI 10.1021/pr900443r) that that morphine induces the producthe proteomes of cultured astrotion of these proteins.) Suder is uncytes also change when morphine sure why his work did not reveal an is administered. increase in interleukins but hypothSuder says the ultimate goal of esizes that the long duration of the the project is to explain how morstudy could be to blame. “The most phine dependence and abstinence Morphine’s influence. Astrocyte proteomics is giving reliable answer, in my opinion, is are established in living organisms. researchers a molecular glimpse of how morphine causes that the interleukins are synthesized “Such discoveries may lead to new addiction. fast and secreted extracellularly,” methods of therapy for drug dewhere the proteins would cause inpendence,” he notes. “Molecular flammation, he says. markers found during investigaSuder explains that it’s still too tions may lead to fast screening to and Suder explains that human material early to say what the up-regulated prodetermine who is more or less suscepis even more complex. “The reason is teins are doing, and additional validation tible to the development of depenthat it is extremely difficult or impossible studies still must be performed. Aside dence.” to find people taking only one subfrom further validation and in vivo studThe brain is the obvious place to start stance,” he points out. ies, Kobaissy suggests that the researchwhen studying drug effects. Historically, The complexity of in vivo systems is ers see whether known glial inhibitors, neurons got all the attention from brain precisely why the researchers should such as propentofylline, suppress the researchers; astrocytes and other glial tackle these types of studies in the near up-regulation of the nine proteins identicells were thought to simply prop up future, notes Firas Kobaissy of the Unified in the study. neurons and keep them in place. Howversity of Florida. The paper “is looking Spijker says that another interesting ever, recent evidence suggests that these at cell culture, which doesn’t mimic experiment would be to co-culture neucells also are major players in various what’s happening in the brain exactly,” rons and astrocytes in a maze-like device neurological processes. For example, ashe states. such that the cells could interact but trocytes are involved in Ca2+ signaling in In the JPR work, morphine was adcould be separated and removed. In this the central nervous system. In addition, ministered to cultured astrocytes for five way, the researchers could determine astrocytes have been implicated in mordays. With 2DE, the researchers comwhether the interactions of neurons and phine activity. In previous studies by pared the proteins expressed by cells astrocytes differ in the presence and abother groups, morphine was shown to treated with morphine and those exsence of morphine, and they could study activate astrocytes, and inhibitors of glial pressed by control cells. The levels of the interdependence of neuronal and nine proteins rose in response to morcells reduced tolerance to the drug. glial regulation. phine, and the levels of two of these To assess morphine’s effects on the —Katie Cottingham were validated by western blotting. The astrocyte proteome, the researchers ISTOCKPHOTO
chose to analyze pure astrocyte cell cultures. “Our experiments are based on purified cells because we believe that the received results are very clear,” says Suder. “The cells answered only to the agent added to the growing medium, and the signal received was free from interferences from other cells in the brain tissue.” Plenty of complicating factors exist when studying whole animals,
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Journal of Proteome Research • Vol. 8, No. 10, 2009
10.1021/pr900759w
© 2009 American Chemical Society
