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
Lysosomal membrane permeabilization (LMP) has emerged as a significant component of cellular signaling pathway by which autophagy or cell death is regulated under many pathological situations including alcohol-associated liver disease (ALD). However, the mechanisms involved in the regulation of LMP in ALD remain obscure. Recently, we demonstrated that lipotoxicity serves as a causal factor to trigger LMP in hepatocytes. We identified that the apoptotic protein BAX (BCL2 associated X, apoptosis regulator) could recruit MLKL (mixed lineage kinase domain-like pseudokinase), a necroptotic executive protein, to lysosomes and induce LMP in various ALD models. Importantly, the pharmacological or genetic inhibition of BAX or MLKL protects hepatocytes from lipotoxicity-induced LMP. Thus, our study reveals a novel molecular mechanism that activation of BAX/MLKL signaling contributes to the pathogenesis of ALD through mediating lipotoxicity-induced LMP. ALD: alcohol-associated liver disease; BAX: BCL2 associated X; LAMP2: lysosomal associated membrane protein 2; LMP: lysosomal membrane permeabilization; MLKL: mixed lineage kinase domain-like pseudokinase; PA: palmitic acid.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062378 | PMC |
http://dx.doi.org/10.1080/15548627.2023.2221989 | DOI Listing |
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