Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Our previous studies have shown that serotonin (5-hydroxytryptamine; 5-HT) is a growth factor for hematopoietic stem/progenitor cells. In this study, we proposed a possible mechanism: 5-HT may enhance megakaryopoiesis and proplatelet formation via Erk1/2 pathway and cytoskeleton reorganization. Here, 5-HT(2B)R was first identified in megakaryocytic cells. 5-HT also promoted the megakaryocytes (MKs) proliferation and reduced the cell apoptosis via the activation of 5-HT(2B)R and Akt pathway. The effects were reduced by the 5-HT2B R inhibitor ketanserin. The effect of 5-HT on proplatelet formation in bone marrow MKs were further confirmed: the 5-HT treated group had more proplatelet bearing MKs compared with the control group. To determine whether 5-HT has effects on cytoskeleton reorganization of MKs, and whether these effects could be reduced by ketanserin or Erk1/2 inhibitor PD98059, MKs were stained with the F-actin specific binder rhodamine-phalloidin. The polymerized actin level was lower in the control group than the 5-HT group and was distributed throughout the cytoplasm with occasional aggregations. Our data demonstrated that Erk1/2 was activated in MKs treated with 5-HT. This study suggests that 5-HT has a potent effect on platelet formation and this effect is likely mediated via 5HT(2B)R with subsequent activation of p-Erk1/2 and consequent F-actin reorganization and proplatelet formation. We also demonstrated that melatonin, the metabolite of 5-HT, exerts a protective effect on MK and platelet recovery in the irradiated mouse model. This study suggested that 5-HT plays an important role in platelet formation via 5HT(2B)R, p-Erk1/2, and F-actin reorganization.
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Source |
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http://dx.doi.org/10.1002/stem.1777 | DOI Listing |
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