Molecular mechanisms of N -acetylcysteine actions

Abstract

Oxidative stress generated by an imbalance between reactive oxygen species (ROS) and antioxidants contributes to the pathogenesis of arthritis, cancer, cardiovascular, liver and respiratory diseases. Proinflammatory cytokines and growth factors stimulate ROS production as signaling mediators. Antioxidants such as N-acetylcysteine (NAC) have been used as tools for investigating the role of ROS in numerous biological and pathological processes. NAC inhibits activation of c-Jun N-terminal kinase, p38 MAP kinase and redox-sensitive activating protein-1 and nuclear factor kappa B transcription factor activities regulating expression of numerous genes. NAC can also prevent apoptosis and promote cell survival by activating extracellular signal-regulated kinase pathway, a concept useful for treating certain degenerative diseases. NAC directly modifies the activity of several proteins by its reducing activity. Despite its nonspecificity, ability to modify DNA and multiple molecular modes of action, NAC has therapeutic value for reducing endothelial dysfunction, inflammation, fibrosis, invasion, cartilage erosion, acetaminophen detoxification and transplant prolongation.

Busulfan-induced senescence is dependent on ROS production upstream of the MAPK pathway

“…The activation of the Erk-p38 MAPK pathway is likely attributable to the oxidative stress induced by BU, because Erk and p38 are sensitive to ROS [16,17,31,36]. It has been shown that the major route of BU metabolism is through GSH-S-transferase catalyzed conjugation to GSH [18,19].…”

“…NAC is a potent antioxidant that can inhibit oxidative stress by directly scavenging ROS and replenishing GSH [31]. If ROS production mediates BU-induced senescence via activation of the Erk-p38 MAPK pathway, we would expect that NAC should have the ability to inhibit BUinduced senescence while suppressing the activity of the Erk-p38 pathway.…”

“…NAC is commonly used as a supplemental substrate for the synthesis of GSH and a scavenger of ROS [30,31]. It has the ability to inhibit oxidative stress induced by various stimuli.…”

Antioxidants and polyunsaturated fatty acids in multiple sclerosis

“…NAC may increase intracellular cysteine and subsequent GSH levels (Deneke, 2000). The molecular mechanism of NAC was recently reviewed (Zafarullah et al, 2003). NAC affects transcription factors, apoptosis and cell survival, all of which are important targets in treating neurodegenerative diseases.…”

Thiol-reducing agents prevent sulforaphane-induced growth inhibition in ovarian cancer cells

“…It has been suggested that caution should be applied when NAC is used as an antioxidant since it also possesses reducing capability via its thiol-disulfide exchange activity independent of its antioxidative or free radical scavenging properties [40,41]. NAC has been shown to prevent apoptosis induced by methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate [42].…”