Augmented cystine-glutamate exchange by pituitary adenylate cyclase-activating polypeptide signaling via the VPAC1 receptor.
Augmented cystine-glutamate exchange by pituitary adenylate cyclase-activating polypeptide signaling via the VPAC1 receptor.
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DOI：
10.1002/syn.21772
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发表时间：
2014-12
期刊：
影响因子：
2.3
通讯作者：
Choi, Sujean
中科院分区：
文献类型：
--
作者：
Resch, Jon M.;Albano, Rebecca;Liu, Xiaoqian;Hjelmhaug, Julie;Lobner, Doug;Baker, David A.;Choi, Sujean
In the central nervous system, cystine import in exchange for glutamate through system xc− is critical for the production of the antioxidant glutathione by astrocytes, as well as the maintenance of extracellular glutamate. Therefore, regulation of system xc− activity affects multiple aspects of cellular physiology and may contribute to disease states. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuronally-derived peptide that has already been demonstrated to modulate multiple aspects of glutamate signaling suggesting PACAP may also target activity of cystine-glutamate exchange via system xc−. In the current study, 24-hour treatment of primary cortical cultures containing neurons and glia with PACAP concentration-dependently increased system xc− function as measured by radiolabeled cystine uptake. Furthermore, the increase in cystine uptake was completely abolished by the system xc− inhibitor, (S)-4-carboxyphenylglycine (CPG), attributing increases in cystine uptake specifically to system xc− activity. Time course and quantitative PCR results indicate that PACAP signaling may increase cystine-glutamate exchange by increasing expression of xCT, the catalytic subunit of system xc−. Furthermore, the potentiation of system xc− activity by PACAP occurs via a PKA-dependent pathway that is not mediated by the PAC1R, but rather the shared vasoactive intestinal polypeptide receptor VPAC1R. Finally, assessment of neuronal, astrocytic, and microglial-enriched cultures demonstrated that only astrocyte-enriched cultures exhibit enhanced cystine uptake following both PACAP and VIP treatment. These data introduce a novel mechanism by which both PACAP and VIP regulate system xc− activity.
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影响因子：
2.5
作者：
Diamond, JS;Jahr, CE
通讯作者：
Jahr, CE
影响因子：
3.5
作者：
Brown, DR
通讯作者：
Brown, DR
DOI：
10.1073/pnas.96.23.13468
发表时间：
1999-11-09
影响因子：
11.1
作者：
Chen, D;Buchanan, GF;Gillette, MU
通讯作者：
Gillette, MU
影响因子：
10.6
作者：
Grant, Jon E.;Kim, Suck Won;Odlaug, Brian L.
通讯作者：
Odlaug, Brian L.
DOI：
10.1111/j.1749-6632.1994.tb19825.x
发表时间：
1994-01-01
期刊：
MODELS OF NEUROPEPTIDE ACTION
影响因子：
--
作者：
ARIMURA, A;SOMOGYVARIVIGH, A;BRENNEMAN, DE
通讯作者：
BRENNEMAN, DE