Recently, autophagy has been found to be strongly activated in colon cancer cells, but few studies have addressed the normal colon mucosa. The aim of this study was to characterize autophagy in normal human intestinal cells. We used the expression of LC3-II and BECN1 as well as SQSTM1 as markers of autophagy activity. Using the normal human intestinal epithelial crypt (HIEC) cell experimental model, we found that autophagy was much more active in undifferentiated cells than in differentiated cells. In the normal adult colonic mucosa, BECN1 was found in the proliferative epithelial cells of the lower part of the gland while SQSTM1 was predominantly found in the differentiated cells of the upper part of the gland and surface epithelium. Interestingly, the weak punctate pattern of SQSTM1 expression in the lower gland colocalized with BECN1-labeled autophagosomes. The usefulness of SQSTM1 as an active autophagy marker was confirmed in colon cancer specimens at the protein and transcript levels. In conclusion, our results show that autophagy is active in the colonic gland and is associated with the intestinal proliferative/undifferentiated and progenitor cell populations.
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http://dx.doi.org/10.4161/auto.19738 | DOI Listing |
Cell Mol Biol Lett
January 2025
University Cote d'Azur, Inserm, C3M, Nice, France.
Vacuolization of hematopoietic precursors cells is a common future of several otherwise non-related clinical settings such as VEXAS, Chediak-Higashi syndrome and Danon disease. Although these disorders have a priori nothing to do with one other from a clinical point of view, all share abnormal vacuolization in different cell types including cells of the erythroid/myeloid lineage that is likely the consequence of moderate to drastic dysfunctions in the ubiquitin proteasome system and/or the endo-lysosomal pathway. Indeed, the genes affected in these three diseases UBA1, LYST or LAMP2 are known to be direct or indirect regulators of lysosome trafficking and function and/or of different modes of autophagy.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany.
Pathological cardiac remodeling is a maladaptive response that leads to changes in the size, structure, and function of the heart. These changes occur due to an acute or chronic stress on the heart and involve a complex interplay of hemodynamic, neurohormonal and molecular factors. As a critical regulator of cell growth, protein synthesis and autophagy mechanistic target of rapamycin complex 1 (mTORC1) is an important mediator of pathological cardiac remodeling.
View Article and Find Full Text PDFNPJ Breast Cancer
January 2025
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Endocrine therapy with CDK4/6 inhibitors is standard for estrogen receptor-positive, HER2-negative metastatic breast cancer (ER+/HER2- MBC), yet clinical resistance develops. Previously, we demonstrated that low doses of palbociclib activate autophagy, reversing initial G1 cell cycle arrest, while high concentrations induce off-target senescence. The autophagy inhibitor hydroxychloroquine (HCQ) induced on-target senescence at lower palbociclib doses.
View Article and Find Full Text PDFFood Chem Toxicol
January 2025
Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning, Guangxi 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. Electronic address:
Objective: The purpose of this work was to investigate whether resveratrol affects lead-induced oxidative damage in HT-22 cells, characterizing mechanisms and strategies for preventing and treating lead-induced neurotoxicity.
Methods: Various lead and resveratrol concentrations were applied to HT-22 cells over different time periods. First, we established the lead treatment (12.
Eur J Oral Sci
January 2025
Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Jeonbuk National University, Jeonju-si, South Korea.
The periodontal ligament (PDL) is a connective tissue, and PDL cells have a potential to differentiate into cementoblasts, osteoblasts, and gingival fibroblasts. This study investigated whether transcription factor c-Myb could induce differentiation of PDL cells for periodontal regeneration. PDL cells were isolated from extracted teeth and cultured.
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