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Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts
Published on: March 22, 2017
Regulation of gene and protein expression in cardiac myocyte hypertrophy and apoptosis
Angela Clerk1, Timothy E Cullingford, Timothy J Kemp
1NHLI Division (Cardiac Medicine Section), Faculty of Medicine, Imperial College London, Flowers Building, Armstrong Road, London SW7 2AZ, UK. a.clerk@imperial.ac.uk
Abstract:
Considerable efforts have been expended in elucidating the inter-cellular and intra-cellular signaling pathways which elicit cardiac myocyte hypertrophy or apoptosis, and in identifying the changes which are associated with the end-stage of the response. The challenge now is to link the two. Although some of the signaling effects will be the acute modulation of existing protein function, long-term effects which bring about and maintain the hypertrophic state or which culminate in cell death are mediated at the level of gene and protein expression. With the advances in micro-array technology and genome sequencing, it is now possible to obtain a picture of the global gene expression profile in myocytes or in whole heart which dictates the proteins which could be made. This is not the final picture since additional regulation at the level of translation modulates the relative proportions of each protein that can be made from the transcriptome. Even here, further regulation of protein stability and turnover means that ultimately it is still necessary to examine the proteome to determine what may cause the functional changes in a cell. Thus, in order to gain a full picture of events which regulate the response and gain some insight into possible points of intervention for therapy, it is necessary to examine gene expression, mRNA translation and protein expression in concert.
Insights
Understanding cardiac myocyte hypertrophy and apoptosis requires integrating gene expression, mRNA translation, and protein expression. This holistic approach is key for identifying therapeutic interventions.
Area of Science:
- Cardiovascular Biology
- Molecular Cell Biology
- Biochemistry
Background:
- Cardiac myocyte hypertrophy and apoptosis are complex cellular responses with significant clinical implications.
- Existing research has focused on inter-cellular and intra-cellular signaling pathways and end-stage changes.
- A critical gap exists in linking signaling pathways to the molecular mechanisms driving these cellular states.
Purpose of the Study:
- To bridge the gap between signaling pathways and the molecular events governing cardiac myocyte hypertrophy and apoptosis.
- To emphasize the necessity of a multi-level analysis encompassing gene, mRNA, and protein expression.
- To identify potential therapeutic intervention points by understanding the complete cellular response.
Main Methods:
- Utilizing advances in micro-array technology and genome sequencing to profile global gene expression.
- Analyzing mRNA translation to understand the modulation of protein synthesis from the transcriptome.
- Examining proteome to determine the final protein complement and its functional consequences.
Main Results:
- Global gene expression profiling provides insights into potential protein synthesis.
- mRNA translation regulation modulates the relative abundance of proteins.
- Protein stability and turnover are critical determinants of the cellular proteome.
Conclusions:
- A comprehensive understanding of cardiac myocyte hypertrophy and apoptosis necessitates the integrated analysis of gene expression, mRNA translation, and protein expression.
- Examining these processes in concert is crucial for elucidating the regulatory events.
- This integrated approach offers potential targets for therapeutic intervention in cardiac diseases.
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