Proteomic analysis of pharmacological preconditioning

Novel protein targets converge to mitochondrial metabolism pathways

D. Kent Arrell, Steven T. Elliott, Lesley A. Kane, Yurong Guo, Young H. Ko, Pete L. Pedersen, John Robinson, Mitsushige Murata, Anne M. Murphy, Eduardo Marbán, Jennifer E. Van Eyk

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Ischemic preconditioning is characterized by resistance to ischemia reperfusion injury in response to previous short ischemic episodes, a protective effect that can be mimicked pharmacologically. The underlying mechanism of protection remains controversial and requires greater understanding before it can be fully exploited therapeutically. To investigate the overall effect of preconditioning on the myocardial proteome, isolated rabbit ventricular myocytes were treated with drugs known to induce preconditioning, adenosine or diazoxide (each at 100 μmol/L for 60 minutes). Their protein profiles were then compared with vehicle-treated controls (n=4 animals per treatment) using a multitiered 2D gel electrophoresis approach. Of 28 significantly altered protein spots, 19 nonredundant proteins were identified (5 spots remained unidentified). The majority of these proteins are involved in mitochondrial energetics, including subunits of tricarboxylic acid cycle enzymes and oxidative phosphorylation complexes. These changes were not indiscriminate, with only a small number of enzymes or complex subunits altered, indicating a very specific and targeted affect of these 2 preconditioning mimetics. Among the changes were shifts in the extent of posttranslational modification of 4 proteins. One of these, the adenosine-induced phosphorylation of the ATP synthase β subunit, was fully characterized with the identification of 5 novel phosphorylation sites. This proteomics approach provides an overall assessment of the cellular response to pharmacological treatment with adenosine and diazoxide and identifies a distinct subset of enzymes and protein complex subunit that may underlie the preconditioned phenotype.

Original languageEnglish
Pages (from-to)706-714
Number of pages9
JournalCirculation Research
Volume99
Issue number7
DOIs
Publication statusPublished - 2006 Oct
Externally publishedYes

Fingerprint

Proteomics
Pharmacology
Adenosine
Diazoxide
Proteins
Enzymes
Myocardial Ischemic Preconditioning
Phosphorylation
Ischemic Preconditioning
Citric Acid Cycle
Oxidative Phosphorylation
Electrophoresis, Gel, Two-Dimensional
Protein Subunits
Proteome
Post Translational Protein Processing
Reperfusion Injury
Muscle Cells
Adenosine Triphosphate
Rabbits
Phenotype

Keywords

  • ATP synthase
  • Phosphorylation
  • Preconditioning
  • Proteomics

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Arrell, D. K., Elliott, S. T., Kane, L. A., Guo, Y., Ko, Y. H., Pedersen, P. L., ... Van Eyk, J. E. (2006). Proteomic analysis of pharmacological preconditioning: Novel protein targets converge to mitochondrial metabolism pathways. Circulation Research, 99(7), 706-714. https://doi.org/10.1161/01.RES.0000243995.74395.f8

Proteomic analysis of pharmacological preconditioning : Novel protein targets converge to mitochondrial metabolism pathways. / Arrell, D. Kent; Elliott, Steven T.; Kane, Lesley A.; Guo, Yurong; Ko, Young H.; Pedersen, Pete L.; Robinson, John; Murata, Mitsushige; Murphy, Anne M.; Marbán, Eduardo; Van Eyk, Jennifer E.

In: Circulation Research, Vol. 99, No. 7, 10.2006, p. 706-714.

Research output: Contribution to journalArticle

Arrell, DK, Elliott, ST, Kane, LA, Guo, Y, Ko, YH, Pedersen, PL, Robinson, J, Murata, M, Murphy, AM, Marbán, E & Van Eyk, JE 2006, 'Proteomic analysis of pharmacological preconditioning: Novel protein targets converge to mitochondrial metabolism pathways', Circulation Research, vol. 99, no. 7, pp. 706-714. https://doi.org/10.1161/01.RES.0000243995.74395.f8
Arrell, D. Kent ; Elliott, Steven T. ; Kane, Lesley A. ; Guo, Yurong ; Ko, Young H. ; Pedersen, Pete L. ; Robinson, John ; Murata, Mitsushige ; Murphy, Anne M. ; Marbán, Eduardo ; Van Eyk, Jennifer E. / Proteomic analysis of pharmacological preconditioning : Novel protein targets converge to mitochondrial metabolism pathways. In: Circulation Research. 2006 ; Vol. 99, No. 7. pp. 706-714.
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