PMID- 24563852
OWN - NLM
STAT- MEDLINE
DCOM- 20150616
LR  - 20211021
IS  - 2213-2317 (Print)
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 2
DP  - 2014
TI  - Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in 
      normal rat kidney (NRK) cells.
PG  - 348-57
LID - 10.1016/j.redox.2014.01.014 [doi]
AB  - Superoxide is widely regarded as the primary reactive oxygen species (ROS) which 
      initiates downstream oxidative stress. Increased oxidative stress contributes, in 
      part, to many disease conditions such as cancer, atherosclerosis, 
      ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese 
      superoxide dismutase (MnSOD) catalyzes the dismutation of superoxide into 
      hydrogen peroxide which can then be further detoxified by other antioxidant 
      enzymes. MnSOD is critical in maintaining the normal function of mitochondria, 
      thus its inactivation is thought to lead to compromised mitochondria. Previously, 
      our laboratory observed increased mitochondrial biogenesis in a novel 
      kidney-specific MnSOD knockout mouse. The current study used transient siRNA 
      mediated MnSOD knockdown of normal rat kidney (NRK) cells as the in vitro model, 
      and confirmed functional mitochondrial biogenesis evidenced by increased PGC1alpha 
      expression, mitochondrial DNA copy numbers and integrity, electron transport 
      chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall 
      ATP production. Further mechanistic studies using mitoquinone (MitoQ), a 
      mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS) 
      inhibitor demonstrated that peroxynitrite (at low micromolar levels) induced 
      mitochondrial biogenesis. These findings provide the first evidence that low 
      levels of peroxynitrite can initiate a protective signaling cascade involving 
      mitochondrial biogenesis which may help to restore mitochondrial function 
      following transient MnSOD inactivation.
FAU - Marine, Akira
AU  - Marine A
AD  - Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock, AR, USA.
FAU - Krager, Kimberly J
AU  - Krager KJ
AD  - Division of Radiation Health, Department of Pharmaceutical Sciences, University 
      of Arkansas for Medical Sciences, Little Rock, AR, USA.
FAU - Aykin-Burns, Nukhet
AU  - Aykin-Burns N
AD  - Division of Radiation Health, Department of Pharmaceutical Sciences, University 
      of Arkansas for Medical Sciences, Little Rock, AR, USA.
FAU - Macmillan-Crow, Lee Ann
AU  - Macmillan-Crow LA
AD  - Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock, AR, USA.
LA  - eng
GR  - R01 DK078936/DK/NIDDK NIH HHS/United States
GR  - R01DK078936./DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140123
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Electron Transport Chain Complex Proteins)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Reactive Oxygen Species)
RN  - 1339-63-5 (Ubiquinone)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 47BYS17IY0 (mitoquinone)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (superoxide dismutase 2)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - DNA, Mitochondrial/metabolism
MH  - Electron Transport Chain Complex Proteins/metabolism
MH  - Gene Knockdown Techniques
MH  - Kidney/*cytology/*metabolism
MH  - Mitochondria/*physiology
MH  - Models, Biological
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Organophosphorus Compounds/pharmacology
MH  - Peroxynitrous Acid/*pharmacology
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxide Dismutase/*genetics/metabolism
MH  - Ubiquinone/analogs & derivatives/pharmacology
PMC - PMC3926114
OTO - NOTNLM
OT  - Mitochondrial biogenesis
OT  - MnSOD
OT  - Peroxynitrite
OT  - Respiration
OT  - mtDNA
OT  - siRNA
EDAT- 2014/02/25 06:00
MHDA- 2014/02/25 06:01
PMCR- 2014/01/23
CRDT- 2014/02/25 06:00
PHST- 2013/12/23 00:00 [received]
PHST- 2014/01/15 00:00 [revised]
PHST- 2014/01/16 00:00 [accepted]
PHST- 2014/02/25 06:00 [entrez]
PHST- 2014/02/25 06:00 [pubmed]
PHST- 2014/02/25 06:01 [medline]
PHST- 2014/01/23 00:00 [pmc-release]
AID - S2213-2317(14)00029-9 [pii]
AID - 10.1016/j.redox.2014.01.014 [doi]
PST - epublish
SO  - Redox Biol. 2014 Jan 23;2:348-57. doi: 10.1016/j.redox.2014.01.014. eCollection 
      2014.