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Thyroid Hormone-Induced Differentiation of Astrocytes is Associated with Transcriptional Upregulation of β-arrestin-1 and β-adrenergic Receptor-Mediated Endosomal Signaling
| Content Provider | Semantic Scholar |
|---|---|
| Author | Das, Moitreyi Ghosh, Mausam Das, Sumantra |
| Copyright Year | 2015 |
| Abstract | Thyroid hormones (TH) promote differentiation of astrocytes. We have previously reported that a downstream role β-adrenergic receptor (β-AR) system in such effects of TH. Although evidences indicate strong interaction between TH and the β-ARs, the underlying mechanism is poorly understood. In the present study, we further explored the influence of TH on β-AR signaling during the differentiation process. Unlike β1-AR, binding of 125I-pindolol to β2-AR in cell membranes was significantly decreased at 2 h of exposure to TH which came back to control values after 24 h. The initial decrease in β2-AR in membranes resulted in a concomitant increase in β2-AR levels in the cytosol, suggesting that TH may induce endocytosis of the receptor. qRT-PCR as well as Western blot analysis demonstrated that unlike β-adrenergic receptor kinase (β-ARK)1 and β-ARK2, the messenger RNA (mRNA) and protein levels of β-arrestin-1 in the astrocyte cultures increased on exposure to TH. Knockdown of β-arrestin gene suggested requirement of both β-arrestin-1 and β-arrestin-2 isoforms during endocytosis of β2-AR, thereby facilitating cell differentiation. Endocytic inhibitors blocked the delayed but sustained activation of p-extracellular signal-regulated kinase (ERK) observed during cell differentiation. Observations suggest that TH upregulate β-arrestin-1 in astrocytes to facilitate endocytosis of β2-AR, required for endosomal ERK activation to drive the differentiation process. |
| Starting Page | 5178 |
| Ending Page | 5190 |
| Page Count | 13 |
| File Format | PDF HTM / HTML |
| DOI | 10.1007/s12035-015-9422-9 |
| PubMed reference number | 26399643 |
| Journal | Medline |
| Volume Number | 53 |
| Alternate Webpage(s) | http://shodhganga.inflibnet.ac.in:8080/jspui/bitstream/10603/171512/13/13_list%20of%20publication.pdf |
| Journal | Molecular Neurobiology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
