PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Lysosome-associated responses”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

3 recordsLinked to original sources
PubMed2026

UVB-aged polystyrene microplastics induce enhanced stress responses in human proximal tubular cells.

Microplastics (MPs) are increasingly detected in human biological matrices, raising concerns about their potential systemic effects, including on the kidney. However, the cellular responses of renal tubular epithelium to MPs and the role of environmental aging processes in modulating their biological activity remain poorly defined. Under environmental conditions, MPs undergo photo-oxidative transformations that alter their surface chemistry and may influence their interactions with biological systems. In this study, we investigated the effects of 1 µm polystyrene MPs in virgin (MPsV) and UVB-oxidised (MPsOx) forms in a human renal proximal tubular cell line (HK-2). Cells were exposed to MPs (25 and 50 µg/mL), and multiple endpoints related to cellular stress and genomic stability were evaluated, including lysosome-associated responses, oxidative damage, DNA integrity, micronucleus formation, DNA-content distribution profiles as an indirect proxy of proliferative status, and cytoskeletal organisation. Exposure to MPs induced measurable stress responses in tubular cells, with oxidised particles generally eliciting stronger effects than MPsV. These responses were consistent with increased oxidative stress, lysosome-associated cellular responses, genomic instability-associated alterations, activation of stress-responsive molecular pathways, and cytoskeletal perturbation. Collectively, these findings indicate that environmentally aged polystyrene MPs elicit more evident cellular stress responses than their virgin counterparts in HK-2 cells. Our results highlight the importance of incorporating environmentally transformed MPs into toxicological testing frameworks to improve the biological relevance of hazard assessment.

Genotoxicity↗
PubMed2026

Hepatitis C Virus Enhances Lysosome-Associated Membrane Protein 2 A Transcription Through Nuclear Factor Erythroid 2-Related Factor 2 to Support Viral Replication.

Hepatitis C virus (HCV) establishes persistent infection by rewiring host stress-response pathways. Chaperone-mediated autophagy (CMA) contributes to HCV replication, but it remains unclear whether HCV regulates lysosome-associated membrane protein 2 A (LAMP-2A), the rate-limiting receptor for CMA. Here, we examined LAMP-2A regulation in HCV-infected Huh-7.5 cells. HCV infection increased LAMP-2A promoter activity, mRNA, and protein abundance, indicating transcriptional upregulation. Among candidate stress-responsive transcription factors, nuclear factor erythroid 2-related factor 2 (NRF2), hypoxia-inducible factor 1α (HIF-1α), and nuclear factor of activated T cells 1 (NFAT1) were elevated in infected cells. However, promoter mutagenesis identified NRF2 as the principal direct regulator. Mutation of the NRF2-responsive antioxidant response element markedly reduced basal and HCV-induced LAMP-2A promoter activity. Chromatin immunoprecipitation assays revealed NRF2 association with the LAMP-2A promoter, and HCV infection increased nuclear accumulation and Ser40 phosphorylation of NRF2. Functionally, shRNA-mediated knockdown of LAMP-2A reduced intracellular HCV RNA and protein levels. These findings identify an NRF2-LAMP-2A regulatory axis engaged during HCV infection and support a model in which HCV upregulates LAMP-2A to establish a cellular environment favorable for viral replication.

Hepacivirus↗
PubMed2026

Amino-acids-mTORC1-driven DDA1 phosphorylation promotes DNA repair and glioblastoma progression.

BACKGROUND: DDA1 is a protein involved in protein degradation, cell cycle regulation, and DNA damage repair. Although its expression varies across tumor types, the precise role of DDA1 in gliomagenesis remains unclear. METHODS: We investigated the function of DDA1 in multiple glioblastoma cell models using biochemical assays, phosphorylation analysis, subcellular localization studies, and integrated genomic and transcriptomic profiling to determine its signaling interactions and downstream effects. RESULTS: We identified a physical association between cytoplasmic DDA1 and Raptor, a core component of lysosome-associated mTORC1. Amino acid stimulation triggered phosphorylation of DDA1 at serine 33 promoting its nuclear translocation and involvement in DNA damage repair. Integrated transcriptomic analyses revealed that the mTORC1-DDA1S33-DNA repair axis regulates the expression of a subset of metabolic genes, including ENO2, CA12, and NMRK1. Functional assays further suggested that these genes contribute to the survival capacity of glioblastoma cells, particularly under DDA1-deficient conditions. Consistently, DDA1 deficiency markedly impaired glioblastoma growth and induced compensatory upregulation of metabolic activity. CONCLUSION: Our findings identify DDA1 as a previously unrecognized phosphorylation target downstream of mTORC1 and a critical mediator of the mTORC1 driven DNA damage response. Through its involvement in DNA repair and metabolic gene regulation, DDA1 appears to support glioblastoma progression, providing mechanistic insight into mTORC1 related gliomagenesis and suggesting potential therapeutic relevance.

Glioblastoma↗