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
Co-exposure to methamphetamine (METH) abuse and HIV infection exacerbates central nervous system damage. However, the underlying mechanisms of this process remain poorly understood. This study aims to explore the roles of neuronal autophagy in the synergistic damage to the central nervous system caused by METH and HIV proteins. Models of METH and HIV-1 Tat protein (Tat) co-exposure were established using tree shrews, primary neurons, and SH-SY5Y cells. Co-exposure to METH and Tat significantly increased the distance traveled, mean velocity, and stereotyped behaviors of tree shrews in the open field test. Western blot analysis revealed that co-exposure to METH and Tat markedly increased the expression of endoplasmic reticulum stress (ERS)-associated proteins (p-ERK, IRE1, ATF6, and Bip) and autophagy markers (ATG7, ATG5, Beclin1, and LC3II). Conversely, co-exposure to METH and Tat significantly downregulated the expressions of p62 and TRIM13. Immunofluorescence staining demonstrated that pretreatment with the ERS inhibitor 4-PBA or siRNA-TRIM13 rescued the abnormal behaviors induced by METH and Tat co-exposure in tree shrews and restored the expression of ERS-related and autophagy-related proteins. Additionally, TRIM13 was found to interact with autophagy-related proteins, including p62, Beclin1, and LC3II by immunoprecipitation assays. Our findings suggest for the first time that METH and Tat synergistically induce neuronal autophagy through ERS pathways, with TRIM13 playing a pivotal regulatory role in this process.
Download full-text PDF |
Source |
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http://dx.doi.org/10.1007/s12035-024-04667-7 | DOI Listing |
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