PMID- 27079272
OWN - NLM
STAT- MEDLINE
DCOM- 20170309
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Apr 15
TI  - Novel Roles for Peroxynitrite in Angiotensin II and CaMKII Signaling.
PG  - 23416
LID - 10.1038/srep23416 [doi]
LID - 23416
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) oxidation controls 
      excitability and viability. While hydrogen peroxide (H2O2) affects 
      Ca(2+)-activated CaMKII in vitro, Angiotensin II (Ang II)-induced CaMKIIdelta 
      signaling in cardiomyocytes is Ca(2+) independent and requires NADPH 
      oxidase-derived superoxide, but not its dismutation product H2O2. To better 
      define the biological regulation of CaMKII activation and signaling by Ang II, we 
      evaluated the potential for peroxynitrite (ONOO(-)) to mediate CaMKII activation 
      and downstream Kv4.3 channel mRNA destabilization by Ang II. In vitro experiments 
      show that ONOO(-) oxidizes and modestly activates pure CaMKII in the absence of 
      Ca(2+)/CaM. Remarkably, this apokinase stimulation persists after mutating known 
      oxidation targets (M281, M282, C290), suggesting a novel mechanism for increasing 
      baseline Ca(2+)-independent CaMKII activity. The role of ONOO(-) in cardiac and 
      neuronal responses to Ang II was then tested by scavenging ONOO(-) and preventing 
      its formation by inhibiting nitric oxide synthase. Both treatments blocked Ang II 
      effects on Kv4.3, tyrosine nitration and CaMKIIdelta oxidation and activation. 
      Together, these data show that ONOO(-) participates in Ang II-CaMKII signaling. 
      The requirement for ONOO(-) in transducing Ang II signaling identifies ONOO(-), 
      which has been viewed as a reactive damaging byproduct of superoxide and nitric 
      oxide, as a mediator of GPCR-CaMKII signaling.
FAU - Zhou, Chaoming
AU  - Zhou C
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
FAU - Ramaswamy, Swarna S
AU  - Ramaswamy SS
AD  - Department of Biochemistry and Molecular Biology and Stark Neuroscience Research 
      Institute, Indiana University School of Medicine, 320 West 15th Street, 
      Indianapolis, IN 46202 USA.
FAU - Johnson, Derrick E
AU  - Johnson DE
AD  - Department of Biochemistry and Molecular Biology and Stark Neuroscience Research 
      Institute, Indiana University School of Medicine, 320 West 15th Street, 
      Indianapolis, IN 46202 USA.
FAU - Vitturi, Dario A
AU  - Vitturi DA
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
FAU - Schopfer, Franciso J
AU  - Schopfer FJ
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
FAU - Freeman, Bruce A
AU  - Freeman BA
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
FAU - Hudmon, Andy
AU  - Hudmon A
AD  - Department of Biochemistry and Molecular Biology and Stark Neuroscience Research 
      Institute, Indiana University School of Medicine, 320 West 15th Street, 
      Indianapolis, IN 46202 USA.
FAU - Levitan, Edwin S
AU  - Levitan ES
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
LA  - eng
GR  - R01 HL132550/HL/NHLBI NIH HHS/United States
GR  - P01 HL103455/HL/NHLBI NIH HHS/United States
GR  - R37 HL058115/HL/NHLBI NIH HHS/United States
GR  - R01HL080632/HL/NHLBI NIH HHS/United States
GR  - R01 HL058115/HL/NHLBI NIH HHS/United States
GR  - R01 HL080632/HL/NHLBI NIH HHS/United States
GR  - NS078171/NS/NINDS NIH HHS/United States
GR  - R01 NS078171/NS/NINDS NIH HHS/United States
GR  - HL64937/HL/NHLBI NIH HHS/United States
GR  - R01 HL064937/HL/NHLBI NIH HHS/United States
GR  - P01-HL103455/HL/NHLBI NIH HHS/United States
GR  - HL058115/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160415
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Reactive Oxygen Species)
RN  - 11128-99-7 (Angiotensin II)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 42HK56048U (Tyrosine)
RN  - AE28F7PNPL (Methionine)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
SB  - IM
MH  - Angiotensin II/*metabolism/pharmacology
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism
MH  - Cell Line
MH  - Methionine/metabolism
MH  - Myocytes, Cardiac/drug effects/metabolism
MH  - Neurons/drug effects/metabolism
MH  - Oxidation-Reduction/drug effects
MH  - Peroxynitrous Acid/*pharmacology
MH  - Phosphorylation
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects
MH  - Tyrosine/metabolism
PMC - PMC4832198
EDAT- 2016/04/16 06:00
MHDA- 2017/03/10 06:00
PMCR- 2016/04/15
CRDT- 2016/04/16 06:00
PHST- 2015/10/13 00:00 [received]
PHST- 2016/03/07 00:00 [accepted]
PHST- 2016/04/16 06:00 [entrez]
PHST- 2016/04/16 06:00 [pubmed]
PHST- 2017/03/10 06:00 [medline]
PHST- 2016/04/15 00:00 [pmc-release]
AID - srep23416 [pii]
AID - 10.1038/srep23416 [doi]
PST - epublish
SO  - Sci Rep. 2016 Apr 15;6:23416. doi: 10.1038/srep23416.