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: 994
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016
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
Phenolic benzotriazole UV stabilizers (BUV) are commonly used additives in synthetic polymeric products, which constantly leak into the environment. They are persistent and bioaccumulative, and have been detected not only in fish, birds, and sea mammals, but also in humans, including breast milk samples. Several authorities including the European Chemical Agency already consider some BUVs as Substances of Very High Concern in need of further information, e.g. mechanistical studies and biomonitoring. In this study, we are addressing this need by investigating the effect of several BUVs on the activity of the human epidermal growth factor receptor (EGFR), an important regulator of cellular processes that has recently been identified as a cell-surface receptor for environmental organic chemicals. By combining in silico docking, mutant analyses, receptor binding and internalization assays, we demonstrate that BUVs, particularly the chlorinated variants, bind to the extracellular domain of EGFR and thereby prevent the binding of growth factors. Accordingly, BUVs can inhibit EGFR downstream events, such as ERK1/2 phosphorylation and DNA synthesis, in human keratinocytes. Our data establish EGFR as a plasma membrane receptor for BUVs, offering novel mechanistic insights into the biological effects induced by these widespread and persistent chemicals. The findings of this study may not only improve hazard assessment for BUVs, but also contribute to the development of novel EGFR-targeting drugs.
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Source |
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http://dx.doi.org/10.1016/j.envint.2024.108886 | DOI Listing |
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