Biomedical Engineering Reference
In-Depth Information
Table 9.31.
Effects of peroxynitrite (Source: [
1147
]). Tetrahydrobiopterin is an essential cofactor
of nitric oxide synthase that carries electrons for redox reactions. Depletion of NOS substrates and
cofactors can prime a feedback (additional peroxynitrite generation).
Target, effect
Examples of targets
Antioxidant enzyme
Superoxide dismutase,
(inhibition)
glutathione reductase, glutaredoxin
Anti-oxidant
Glutathione, cysteine
(depletion)
Cytosolic enzyme
creatine kinase, Tyr phosphatases,
(inhibition)
Tyr hydroxylase
Protein aggregation
Microtubule-associated protein Tau
Enzyme activation
Fibrinogen, matrix metalloproteinases,
cytochrome-C, glutathione-S-transferase,
PKC
Enzyme cofactor impairment
Tetrahydrobiopterin (BH4), NADH
Calcium pumps, Na
+
-K
+
AT P a s e ,
Membrane channel
(inhibition)
sodium channels, Ca
V
1
Signaling messengers
FGF, IL8/10, NGF,
Receptors
β
-adrenoceptors, A
1
(adenosine),
HER, insulin receptor
Calcium
Signaling mediators
Prostacylin synthase, cyclooxygenases,
AMPK, MAPK, Src, PKC, PI3K
Transcriptional regulators
PPAR
(NR1c3), STAT3 (VEGF axis),
HDAC2 (nitration [inactivation])
γ
Adhesion molecules
ICAM1, selectins, integrins
Surfactant proteins
Lipids, arachidonic acid
Low-density lipoproteins
DNA injury
Genotoxicity, cell death
Mitochondrial dysfunction
Impaired mitochondrial respiration
and lipid and protein nitration. Moreover, ONOOH in membranes can react with
thiols (2-electron oxidation that forms NO
2
and sulphenic acid derivatives [RSOH]
often converted to disulphides [R
(
1
)
SSR
(
2
)
]) and metal centers.
186
Transient ONOOCO
2
adduct that results from the reaction between ONOO
−
and
CO
2
in aqueous phase also creates either NO
3
(isomerization;
∼
2/3 reactions) or
•
OH) and NO
2
radicals (homolysis;
1/3 reactions) [
1147
].
Peroxynitrite can influence cell signaling (especially apoptosis) and mitochon-
drial function and cause cell death (Table
9.31
). Although peroxynitrite exert various
cytotoxic effects mainly due to oxidation and nitration reactions, it can lead to the
∼
186
Resulting oxometals can trigger secondary free-radical reactions.
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