Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Oxidative stress predisposes to several aging-associated diseases, such as cardiovascular diseases and cancer. In aging, increase in the production of reactive oxygen species is typically accompanied with a decline in adaptive stress responses to oxidative stress. The decline is primarily due to a decrease in antioxidant production. Nuclear factor E2-Related Factor 2 (NRF2) is a key transcription factor regulating oxidative and electrophilic stress responses, but it has also been shown to play a role in the regulation of cell metabolism. NRF2 expression declines in aging, but the mechanisms remain unclear. In this study, we show that microRNAs (miRNAs) that are abundant in old endothelial cells decrease NRF2 expression by direct targeting of NRF2 mRNA. The effect is reversed by miRNA inhibition. The senescence-associated downregulation of NRF2 decreases endothelial glycolytic activity and stress tolerance both of which are restored after reinstating NRF2. Manipulation of the senescence-associated miRNA levels affects the glycolytic activity and stress tolerance consistently with the NRF2 results. We conclude that senescence-associated miRNAs are involved in the decline of NRF2 expression, thus contributing to the repression of adaptive responses during cell senescence.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037909 | PMC |
http://dx.doi.org/10.1016/j.redox.2018.06.007 | DOI Listing |
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