Proteomic and metabolomic analysis of cardioprotection: Interplay between protein kinase C epsilon and delta in regulating glucose metabolism of murine hearts.
Proteomic and metabolomic analysis of cardioprotection: Interplay between protein kinase C epsilon and delta in regulating glucose metabolism of murine hearts.
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DOI：
10.1016/j.yjmcc.2008.10.008
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发表时间：
2009-02
影响因子：
5
通讯作者：
Ping, Peipei
中科院分区：
文献类型：
--
作者：
Mayr, Manuel;Liem, David;Zhang, Jun;Li, Xiaohai;Avliyakuiov, Nuraly K.;Yang, Jeong In;Young, Glen;Vondriska, Tom M.;Ladroue, Christophe;Madhu, Basetti;Griffiths, John R.;Gomes, Aldrin;Xu, Qingbo;Ping, Peipei
We applied a combined proteomic and metabolomic approach to obtain novel mechanistic insights in PKCε-mediated cardioprotection. Mitochondrial and cytosolic proteins from control and transgenic hearts with constitutively active or dominant negative PKCε were analyzed using difference in-gel electrophoresis (DIGE). Among the differentially expressed proteins were creatine kinase, pyruvate kinase, lactate dehydrogenase, and the cytosolic isoforms of aspartate amino transferase and malate dehydrogenase, the two enzymatic components of the malate aspartate shuttle, which is required for the import of reducing equivalents from glycolysis across the inner mitochondrial membrane. These enzymatic changes appeared to be dependent on PKCε activity, as they were not observed in mice expressing inactive PKCε. High-resolution proton nuclear magnetic resonance (1H-NMR) spectroscopy confirmed a pronounced effect of PKCε activity on cardiac glucose and energy metabolism: normoxic hearts with constitutively active PKCε had significantly lower concentrations of glucose, lactate, glutamine and creatine, but higher levels of choline, glutamate and total adenosine nucleotides. Moreover, the depletion of cardiac energy metabolites was slower during ischemia/reperfusion injury and glucose metabolism recovered faster upon reperfusion in transgenic hearts with active PKCε. Notably, inhibition of PKCε resulted in compensatory phosphorylation and mitochondrial translocation of PKCδ. Taken together, our findings are the first evidence that PKCε activity modulates cardiac glucose metabolism and provide a possible explanation for the synergistic effect of PKCδ and PKCε in cardioprotection.
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影响因子：
24
作者：
Mayr, Manuel;Yusuf, Shamil;Camm, A. John
通讯作者：
Camm, A. John
DOI：
10.1073/pnas.191369098
发表时间：
2001-09-25
影响因子：
11.1
作者：
Chen, L;Hahn, H;Mochly-Rosen, D
通讯作者：
Mochly-Rosen, D
影响因子：
20.1
作者：
Churchill, EN;Murriel, CL;Szweda, LI
通讯作者：
Szweda, LI
DOI：
10.1152/ajpheart.2001.280.3.h1346
发表时间：
2001-03-01
影响因子：
4.8
作者：
Fryer, RM;Wang, YG;Gross, GJ
通讯作者：
Gross, GJ
影响因子：
9.5
作者：
Fryer, RM;Hsu, AK;Gross, GJ
通讯作者：
Gross, GJ