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Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
First Glance at Myeloid Leukaemia Factor 2 in Cardiomyocytes
Jakob Christoph Voran1,2, Lucia Sophie Kilian1,2, Simone Martini1,2
1Department of Internal Medicine III, Cardiology and Critical Care, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Insights
Myeloid leukaemia factor 2 (MLF2) is implicated in heart failure by accumulating in protein aggregates and interacting with alphaB-crystallin. MLF2 upregulation may protect against cardiomyocyte hypertrophy and heart failure.
Area of Science:
- Cardiology
- Molecular Biology
- Protein Homeostasis
Background:
- Protein homeostasis is vital for cardiomyocyte function and survival, with chaperones, the ubiquitin-proteasome system, and autophagy as key regulators.
- Protein aggregates in desmin-related cardiomyopathies (DRM) and associations with dilated cardiomyopathy (DCM) highlight potential molecular players.
- Myeloid leukaemia factor 2 (MLF2) is identified as a protein of interest due to its presence in cardiac protein aggregates.
Purpose of the Study:
- To investigate the role of myeloid leukaemia factor 2 (MLF2) in maintaining protein homeostasis within cardiomyocytes.
- To explore the potential interaction between MLF2 and alphaB-crystallin (CryAB).
- To determine the functional significance of MLF2 in cardiac hypertrophy and heart failure models.
Main Methods:
- Proteomic analysis to identify proteins within cardiac aggregates.
- Co-immunoprecipitation assays to assess protein-protein interactions.
- Quantitative real-time PCR to measure MLF2 gene expression in heart failure and hypertrophy models.
- Overexpression studies in vitro to evaluate the functional impact of MLF2.
Main Results:
- MLF2 was found to be overrepresented in protein aggregates in mouse models of desmin-related cardiomyopathies (DRM).
- AlphaB-crystallin (CryAB) was identified as a potential interaction partner of MLF2.
- MLF2 expression was significantly upregulated in mouse models of heart failure and in vitro models of cardiomyocyte hypertrophy.
- Overexpression of MLF2 attenuated pro-hypertrophic gene expression, suggesting a protective role.
Conclusions:
- MLF2 plays a role in regulating protein homeostasis in cardiomyocytes.
- MLF2 may interact with alphaB-crystallin (CryAB).
- MLF2 exhibits a functional role in modulating hypertrophic signaling pathways, potentially offering protection against heart failure progression.
Abstract:
Understanding the molecular mechanisms that maintain protein homeostasis in cardiomyocytes is fundamental for the development of causal therapies for heart failure. Chaperones, the ubiquitin-proteasome system and autophagy are major regulators of cardiac homeostasis and are crucial for cardiomyocyte function and survival. In this context, myeloid leukaemia factor 2 (MLF2) emerged as a candidate of interest, as we found it overrepresented in protein aggregates in the hearts of mouse models of desmin-related cardiomyopathies (DRM), and it has also been suggested to be associated with dilated cardiomyopathy (DCM). Here, we identified αB-crystallin (CryAB), among other proteins, as a potential interaction partner of MLF2. Functionally, MLF2 was significantly upregulated in mouse models of heart failure and in two in vitro models of cardiomyocyte hypertrophy, and its overexpression resulted in attenuation of pro-hypertrophic gene expression. Taken together, these findings provide initial evidence supporting a role for MLF2 in regulating protein homeostasis and in modulating hypertrophic signalling in cardiomyocytes.
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