The p62 protein has been identified as a major component of the protein aggregations associated with neurodegenerative disease. Oxidative insult has also been identified as a principal cause of neurodegenerative disease. Thus, in the present study, we investigated the potential role of p62 in oxidative stress-induced cell death in SH-SY5Y human neuroblastoma cells. The results indicated that H(2)O(2) treatment induced p62 expression in SH-SY5Y cells. In addition, p62 showed neuroprotective effects against H(2)O(2)-induced cell death in differentiated SH-SY5Y cells. p62 expression prolonged Akt phosphorylation during the later stages of H(2)O(2)-induced cell death. Furthermore, coexpression of p62 and wild-type PDK1, the upstream kinase of Akt, further increased Akt phosphorylation and cell viability, whereas the expression of kinase-defective PDK1 reversed the cytoprotective effects of p62 under oxidative stress. Overexpression of p62 led to the dissociation of PDK1 from the 14-3-3theta protein, which is thought to be a negative regulator of PDK1 kinase activity. These findings suggest a mechanism that involves the p62-mediated modulation of the interaction between signaling molecules and results in cell survival.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neulet.2008.11.011 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The transcription factor YbdO attenuates the pathogenicity of avian pathogenic Escherichia coli by regulating oxidative stress response.
BMC Microbiol
December 2024
College of Agriculture and Forestry, Linyi University, Linyi, 276005, Shandong, China.
Avian pathogenic Escherichia coli (APEC) is a significant pathogen infecting poultry that is responsible for high mortality, morbidity and severe economic losses to the poultry industry globally, posing a substantial risk to the health of poultry. APEC encounters reactive oxygen species (ROS) during the infection process and thus has evolved antioxidant defense mechanisms to protect against oxidative damage. The imbalance of ROS production and antioxidant defenses is known as oxidative stress, which results in oxidative damage to proteins, lipids and DNA, and even bacterial cell death.
View Article and Find Full Text PDFMicroglia-like cells from patient monocytes demonstrate increased phagocytic activity in probable Alzheimer's disease.
Mol Cell Neurosci
December 2024
Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Türkiye; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Türkiye; Department of Neuroscience, Institute of Health Sciences, Dokuz Eylul University, Izmir, Türkiye. Electronic address:
Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by the accumulation of amyloid plaques, phosphorylated tau tangles and microglia toxicity, resulting in neuronal death and cognitive decline. Since microglia are recognized as one of the key players in the disease, it is crucial to understand how microglia operate in disease conditions and incorporate them into models. The studies on human microglia functions are thought to reflect the post-symptomatic stage of the disease.
View Article and Find Full Text PDFSelf-assembled natural triterpenoids for the delivery of cyclin-dependent kinase 4/6 inhibitors to enhance cancer chemoimmunotherapy.
J Control Release
December 2024
Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng 475000, PR China; State Key Laboratory of Antiviral Drugs, Henan University, Kaifeng 475000, PR China; Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, PR China. Electronic address:
Immunogenic cell death (ICD) has recently emerged as a promising strategy in reinforcing anti-PD-L1 blockade immunotherapy of triple-negative breast cancer (TNBC). The CDK4/6 inhibitor palbociclib (PAL), as a clinical star medicine targeting the cell cycle machinery, is an ideal candidate for fabricating a highly efficient ICD inducer for TNBC chemoimmunotherapy. However, the frequently observed chemoresistance and clinical adverse effects, as well as significant antagonistic effects when co-administered with certain chemotherapeutics, have seriously restricted the efficiency of PAL and the feasibility of combination strategies.
View Article and Find Full Text PDFA3AR antagonism mitigates metabolic dysfunction-associated steatotic liver disease by exploiting monocyte-derived Kupffer cell necroptosis and inflammation resolution.
Metabolism
December 2024
College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk, South Korea. Electronic address:
Background & Aims: Metabolic dysfunction-associated steatotic liver (MASLD) progression is driven by chronic inflammation and fibrosis, largely influenced by Kupffer cell (KC) dynamics, particularly replenishment of pro-inflammatory monocyte-derived KCs (MoKCs) due to increased death of embryo-derived KCs. Adenosine A3 receptor (A3AR) plays a key role in regulating metabolism and immune responses, making it a promising therapeutic target. This study aimed to investigate the impact of selective A3AR antagonism for regulation of replenished MoKCs, thereby improving MASLD.
View Article and Find Full Text PDFLoss-of-function SLC25A20 mutation causes carnitine-acylcarnitine translocase deficiency by reducing SLC25A20 protein stability.
Gene
December 2024
Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou 510515, China; Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China. Electronic address:
Background/aim: Autosomal-recessive carnitine-acylcarnitine translocase deficiency (CACTD) is a rare disorder of long-chain fatty acid oxidation caused by variants in the SLC25A20 gene. Under fasting conditions, most newborns with severe CACTD experience sudden cardiac arrest and hypotonia, often leading to premature death due to rapid disease progression. Understanding of genetic factors and pathogenic mechanisms in CACTD is essential for its diagnosis, treatment, and prevention.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!