Regulation of gene and protein expression in cardiac myocyte hypertrophy and apoptosis.
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.
Clerk
Angela
A
NHLI Division (Cardiac Medicine Section), Faculty of Medicine, Imperial College London, Flowers Building, Armstrong Road, London SW7 2AZ, UK. a.clerk@imperial.ac.uk
Cullingford
Timothy E
TE
Kemp
Timothy J
TJ
Kennedy
Robert A
RA
Sugden
Peter H
PH
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006984:Hypertrophy / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology*; D010544:Peroxidases / Q000096:biosynthesis; D054464:Peroxiredoxins; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D006360:Heat-Shock Proteins; D010544:Peroxidases; C489898:Prdx1 protein, rat; D054464:Peroxiredoxins