Glial cell line-derived neurotrophic factor (GDNF) enhances dopamine release from striatal nerve endings in an adenosine A2A receptor-dependent manner

2006 ◽  
Vol 1113 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Catarina A.R.V. Gomes ◽  
Sandra H. Vaz ◽  
Joaquim A. Ribeiro ◽  
Ana M. Sebastião
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopamine Release ◽  
Adenosine A2a Receptor ◽  
Nerve Endings ◽  
Dependent Manner ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals Adenosine A2A receptor signaling promotes FoxO associated autophagy in chondrocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin Friedman ◽  
Carmen Corciulo ◽  
Cristina M. Castro ◽  
Bruce N. Cronstein
Keyword(s):  
Cell Line ◽  
Metabolic Stress ◽  
Human Cell Line ◽  
Adenosine A2a Receptor ◽  
Autophagic Flux ◽  
A2a Receptor ◽  
Adenosine A2a ◽  
A2ar Agonist

AbstractAutophagy, a homeostatic pathway upregulated during cellular stress, is decreased in osteoarthritic chondrocytes and this reduction in autophagy is thought to contribute to the development and progression of osteoarthritis (OA). The adenosine A2A receptor (A2AR) is a potent anti-inflammatory receptor and deficiency of this receptor leads to the development of OA in mice. Moreover, treatment using liposomally conjugated adenosine or a specific A2AR agonist improved joint scores significantly in both rats with post-traumatic OA (PTOA) and mice subjected to a high fat diet obesity induced OA. Importantly, A2AR ligation is beneficial for mitochondrial health and metabolism in vitro in primary and the TC28a2 human cell line. An additional set of metabolic, stress-responsive, and homeostatic mediators include the Forkhead box O transcription factors (FoxOs). Data has shown that mouse FoxO knockouts develop early OA with reduced cartilage autophagy, indicating that FoxO-induced homeostasis is important for articular cartilage. Given the apparent similarities between A2AR and FoxO signaling, we tested the hypothesis that A2AR stimulation improves cartilage function through activation of the FoxO proteins leading to increased autophagy in chondrocytes. We analyzed the signaling pathway in the human TC28a2 cell line and corroborated these findings in vivo in a metabolically relevant obesity-induced OA mouse model. We found that A2AR stimulation increases activation and nuclear localization of FoxO1 and FoxO3, promotes an increase in autophagic flux, improves metabolic function in chondrocytes, and reduces markers of apoptosis in vitro and reduced apoptosis by TUNEL assay in vivo. A2AR ligation additionally enhances in vivo activation of FoxO1 and FoxO3 with evidence of enhanced autophagic flux upon injection of the liposome-associated A2AR agonist in a mouse obesity-induced OA model. These findings offer further evidence that A2AR may be an excellent target for promoting chondrocyte and cartilage homeostasis.

scholarly journals Glial Cell Line-Derived Neurotrophic Factor: An Intraovarian Factor that Enhances Oocyte Developmental Competence in Vitro

Endocrinology ◽  
2007 ◽  
Vol 148 (9) ◽  
pp. 4292-4301 ◽  
Author(s):  
Katja Linher ◽  
De Wu ◽  
Julang Li
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Preimplantation Embryo ◽  
Cyclin B1 ◽  
Developmental Competence ◽  
Dependent Manner ◽  
Nuclear Maturation ◽  
Cytoplasmic Maturation

The success of early embryonic development depends on oocyte nuclear and cytoplasmic maturation. We have investigated whether glial cell line-derived neurotrophic factor (GDNF) affects the in vitro maturation (IVM) of porcine oocytes and their subsequent ability to sustain preimplantation embryo development. GDNF and both its coreceptors, GDNF family receptor α-1 (GFRα-1) and the rearranged during transformation (RET) receptor, were expressed in oocytes and their surrounding cumulus cells derived from small and large follicles. When included in IVM medium, GDNF significantly enhanced cumulus cell expansion of both small and large cumulus-oocyte complexes and increased the percentage of small follicle-derived oocytes maturing to the metaphase II stage, although nuclear maturation of large oocytes was not significantly affected. Examination of cyclin B1 protein expression as a measure of cytoplasmic maturation revealed that in the presence of GDNF, cyclin B1 levels were significantly increased in large follicle-derived oocytes, as well as in oocytes from small follicles to a level comparable to the untreated large group. After activation, a significantly higher percentage of both small and large oocytes that were matured in the presence of GDNF developed to the blastocyst stage compared with untreated controls. Indeed, GDNF enhanced the blastocyst rate of small oocytes to levels comparable to those obtained for large oocytes matured without GDNF. The effect of GDNF was specific; this was evident because its enhancement of nuclear maturation and embryo developmental potential was blocked by an antibody against GFRα-1. Our study provides the first functional evidence that GDNF affects oocyte maturation and preimplantation embryo developmental competence in a follicular stage-dependent manner. This finding may provide insights for improving the formulation of IVM culture systems, especially for oocytes from small follicles.

scholarly journals Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells

2019 ◽  
Vol 21 (1) ◽  
pp. 253 ◽  
Author(s):  
Yoshiko Furukawa ◽  
Ryu-ichi Hara ◽  
Makiko Nakaya ◽  
Satoshi Okuyama ◽  
Atsushi Sawamoto ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Specific Inhibitor ◽  
C6 Glioma Cells ◽  
Dependent Manner ◽  
C6 Cells ◽  
Anti Inflammatory ◽  
The Brain

We previously demonstrated that auraptene (AUR), a natural coumarin derived from citrus plants, exerts anti-inflammatory effects in the brain, resulting in neuroprotection in some mouse models of brain disorders. The present study showed that treatment with AUR significantly increased the release of glial cell line-derived neurotrophic factor (GDNF), in a dose- and time-dependent manner, by rat C6 glioma cells, which release was associated with increased expression of GDNF mRNA. These results suggest that AUR acted as a neuroprotective agent in the brain via not only its anti-inflammatory action but also its induction of neurotrophic factor. We also showed that (1) the AUR-induced GDNF production was inhibited by U0126, a specific inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) 1/2, and by H89, a specific inhibitor of protein kinase A (PKA); and (2) AUR induced the phosphorylation of cAMP response element-binding protein (CREB), a transcription factor located within the nucleus. These results suggest that AUR-stimulated gdnf gene expression was up-regulated through the PKA/ERK/CREB pathway in C6 cells.

scholarly journals Human Adenosine A2A Receptor Binds Calmodulin with High Affinity in a Calcium-Dependent Manner

2015 ◽  
Vol 108 (4) ◽  
pp. 903-917 ◽  
Author(s):  
Henni Piirainen ◽  
Maarit Hellman ◽  
Helena Tossavainen ◽  
Perttu Permi ◽  
Petri Kursula ◽  
...  
Keyword(s):  
Adenosine A2a Receptor ◽  
Dependent Manner ◽  
Calcium Dependent ◽  
High Affinity ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals Glial Cell Line–Derived Neurotrophic Factor Receptor Rearranged During Transfection Agonist Supports Dopamine Neurons In Vitro and Enhances Dopamine Release In Vivo

2019 ◽  
Vol 35 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Arun Kumar Mahato ◽  
Jaakko Kopra ◽  
Juho‐Matti Renko ◽  
Tanel Visnapuu ◽  
Ilari Korhonen ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopamine Release ◽  
Dopamine Neurons
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