Effect of human equilibrative nucleoside transporter 1 (hENT1) and ecto-5' nucleotidase (eN) in adenosine formation by neurons and astrocytes under ischemic conditions.
| dc.contributor.author | Chu, Stephanie S.T.Y. | |
| dc.contributor.examiningcommittee | Miller, Don (Pharmacology & Therapeutics) Anderson, Chris (Pharmacology & Therapeutics) Kong, Jiming (Human Anatomy & Cell Science) | en_US |
| dc.contributor.supervisor | Parkinson, Fiona (Pharmacology & Therapeutics) | en_US |
| dc.date.accessioned | 2012-08-17T13:15:32Z | |
| dc.date.available | 2012-08-17T13:15:32Z | |
| dc.date.issued | 2012-08-17 | |
| dc.degree.discipline | Pharmacology and Therapeutics | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Adenosine (ADO) is an endogenous neuroprotectant. Under ischemic conditions ADO levels rise in the brain up to 100-fold. ADO in the brain is dependent on the movement across cell membranes by equilibrative nucleoside transporters (ENT) or produced from membrane bound ecto-5’ nucleotidase (eN). We used transgenic neurons with neuronal specific expression of human ENT1 (hENT1) and eN knockout (CD73 KO) astrocytes. The aim of this research was to determine the role of ENT1 and eN in ADO release from ischemic-like conditions in primary cultured neurons, astrocytes or co-cultures. Neurons primarily release intracellular ADO via ENTs; this effect was blocked by transporter inhibitor, dipyridamole (DPR). Astrocytes primarily convert ADO extracellularly from eN; this effect was with eN inhibitor α, β-methylene ADP (AOPCP). Combined neuron and KO astrocytes produced less ADO, extracellular ADO was inhibited by DPR but not AOPCP. Overall these results suggest that eN is prominent in the formation of ADO but other enzymes or pathways contribute to rising ADO levels in ischemic conditions. | en_US |
| dc.description.note | October 2012 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/8353 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Adenosine | en_US |
| dc.subject | human equilibrative nucleoside transporter (hENT1) | en_US |
| dc.subject | ecto 5' nucleotidase (CD73) | en_US |
| dc.subject | cerebral ischemia | en_US |
| dc.subject | NMDA | en_US |
| dc.subject | neuron | en_US |
| dc.subject | astrocyte | en_US |
| dc.subject | cell culture | en_US |
| dc.subject | oxygen-glucose deprivation | en_US |
| dc.title | Effect of human equilibrative nucleoside transporter 1 (hENT1) and ecto-5' nucleotidase (eN) in adenosine formation by neurons and astrocytes under ischemic conditions. | en_US |
| dc.type | master thesis | en_US |