PMID- 16303765
OWN - NLM
STAT- MEDLINE
DCOM- 20060307
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 4
DP  - 2006 Jan 27
TI  - Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function 
      and augments hypoxia and myocardial ischemia-related injury.
PG  - 2061-70
AB  - We have investigated the effects of hypoxia and myocardial ischemia/reperfusion 
      on the structure and function of cytochrome c oxidase (CcO). Hypoxia (0.1% O(2) 
      for 10 h) and cAMP-mediated inhibition of CcO activity were accompanied by 
      hyperphosphorylation of subunits I, IVi1, and Vb and markedly increased reactive 
      O(2) species production by the enzyme complex in an in vitro system that uses 
      reduced cytochrome c as an electron donor. Both subunit phosphorylation and 
      enzyme activity were effectively reversed by 50 nm H89 or 50 nm myristoylated 
      peptide inhibitor (MPI), specific inhibitors of protein kinase A, but not by 
      inhibitors of protein kinase C. In rabbit hearts subjected to global and focal 
      ischemia, CcO activity was inhibited in a time-dependent manner and was 
      accompanied by hyperphosphorylation as in hypoxia. Additionally, CcO activity and 
      subunit phosphorylation in the ischemic heart were nearly completely reversed by 
      H89 or MPI added to the perfusion medium. Hyperphosphorylation of subunits I, 
      IVi1, and Vb was accompanied by reduced subunit contents of the 
      immunoprecipitated CcO complex. Most interestingly, both H89 and MPI added to the 
      perfusion medium dramatically reduced the ischemia/reperfusion injury to the 
      myocardial tissue. Our results pointed to an exciting possibility of using CcO 
      activity modulators for controlling myocardial injury associated with ischemia 
      and oxidative stress conditions.
FAU - Prabu, Subbuswamy K
AU  - Prabu SK
AD  - Department of Animal Biology, School of Veterinary Medicine, University of 
      Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
FAU - Anandatheerthavarada, Hindupur K
AU  - Anandatheerthavarada HK
FAU - Raza, Haider
AU  - Raza H
FAU - Srinivasan, Satish
AU  - Srinivasan S
FAU - Spear, Joseph F
AU  - Spear JF
FAU - Avadhani, Narayan G
AU  - Avadhani NG
LA  - eng
GR  - R01 GM049683/GM/NIGMS NIH HHS/United States
GR  - GM 49683/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20051122
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Isoquinolines)
RN  - 0 (Peptides)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sulfonamides)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Carbon Monoxide
MH  - Cells, Cultured
MH  - Cyclic AMP-Dependent Protein Kinases/chemistry/metabolism/*physiology
MH  - Electron Transport Complex IV/*metabolism
MH  - *Hypoxia
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Ischemia/*pathology
MH  - Isoquinolines/pharmacology
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Monocytes/metabolism
MH  - Myocardial Ischemia
MH  - Myocardium/*pathology
MH  - Oxidative Stress
MH  - Oxygen/metabolism
MH  - Peptides/chemistry
MH  - Perfusion
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Rabbits
MH  - Reactive Oxygen Species
MH  - Reperfusion Injury
MH  - Sulfonamides/pharmacology
MH  - Time Factors
PMC - PMC4271455
MID - NIHMS515873
EDAT- 2005/11/24 09:00
MHDA- 2006/03/08 09:00
PMCR- 2014/12/19
CRDT- 2005/11/24 09:00
PHST- 2005/11/24 09:00 [pubmed]
PHST- 2006/03/08 09:00 [medline]
PHST- 2005/11/24 09:00 [entrez]
PHST- 2014/12/19 00:00 [pmc-release]
AID - S0021-9258(20)70757-X [pii]
AID - 10.1074/jbc.M507741200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Jan 27;281(4):2061-70. doi: 10.1074/jbc.M507741200. Epub 2005 
      Nov 22.