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Production and Characterization of K562 Cellular Clones Hyper-Expressing the Gene Encoding α-Globin: Preliminary Analysis of Biomarkers Associated with Autophagy.
- Source :
- Genes; Mar2023, Vol. 14 Issue 3, p556, 16p
- Publication Year :
- 2023
-
Abstract
- One of the most relevant pathophysiological hallmarks of β-thalassemia is the accumulation of toxic α-globin chains inside erythroid cells, which is responsible for their premature death (hemolysis). In this context, the availability of an experimental model system mimicking the excess in α-globin chain production is still lacking. The objective of the present study was to produce and characterize K562 cellular clones forced to produce high amounts of α-globin, in order to develop an experimental model system suitable for studies aimed at the reduction of the accumulation of toxic α-globin aggregates. In the present study, we produced and characterized K562 cellular clones that, unlike the original K562 cell line, stably produced high levels of α-globin protein. As expected, the obtained clones had a tendency to undergo apoptosis that was proportional to the accumulation of α-globin, confirming the pivotal role of α-globin accumulation in damaging erythroid cells. Interestingly, the obtained clones seemed to trigger autophagy spontaneously, probably to overcome the accumulation/toxicity of the α-globin. We propose this new model system for the screening of pharmacological agents able to activate the full program of autophagy to reduce α-globin accumulation, but the model may be also suitable for new therapeutical approaches targeted at the reduction of the expression of the α-globin gene. [ABSTRACT FROM AUTHOR]
- Subjects :
- MOLECULAR cloning
GLOBIN genes
AUTOPHAGY
BIOMARKERS
GENE expression
EARLY death
Subjects
Details
- Language :
- English
- ISSN :
- 20734425
- Volume :
- 14
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Genes
- Publication Type :
- Academic Journal
- Accession number :
- 162815456
- Full Text :
- https://doi.org/10.3390/genes14030556