. Author manuscript; available in PMC: 2008 Feb 4.

Published in final edited form as: Trends Pharmacol Sci. 2005 Jun;26(6):302–310. doi: 10.1016/j.tips.2005.04.003

Table 1.

Cytotoxic processes initiated by peroxynitrite in vitro

Action	Mechanism(s)
Lipid peroxidation	Peroxidation
Inhibition and depletion of antioxidant enzymes	Oxidation and nitration of glutathione and cysteine (required by antioxidant enzymes)
Activation of matrix metalloproteinases (MMPs)	S-Glutathiolation of pro-matrix metalloproteinases
Disturbances of signal transduction pathways	Oxidation and nitration of various proteins
Mitochondrial dysfunction	Inhibition of, for example, cytochromes and NADH-CoQ1 reductase (complex I)
Inhibition of cytosolic enzymes and membrane pumps	Oxidation and nitration of various proteins
Ca²⁺ dysregulation	Inhibition of ion pumps (e.g. Ca²⁺ pumps, Ca²⁺-activated K⁺ channels and Na⁺–K⁺-ATPase, leading to dysfunctional cell energetics
Contractile protein dysfunction	Oxidation and nitration of contractile proteins
Upregulation of adhesion receptors	Activation of NF-κB
DNA injury and PARP activation	Oxidation and nitration of various proteins
Inhibition of NAD-dependent enzymes	NAD oxidation, and NAD depletion via PARP
Apoptosis	Mitochondrial injury, DNA injury, caspase activation, signal transduction disturbances and Ca²⁺ dysregulation
Cell necrosis	Mitochondrial injury, energetic collapse, oxidation, nitration, antioxidant depletion and Ca²⁺ dysregulation