Components involved in apoptosis | Basal function | Effects after oxidative regulation | Ref |
---|---|---|---|
Transcriptional level | |||
 NF-κB | NF-κB as a transcription factor activates transcription of target genes, such as elevated expression of anti-apoptotic Bcl2 family (Bcl-XL), FLIP, caspase inhibitors (XIAP) | ROS↑ activation of NF-κB↑ anti-apoptotic protein expression ↑ | [77] |
 Nrf2 | Nrf2 regulates the transcription of genes, the protein of these genes have antioxidant and glutathione synthase functions and can defend against oxidative stress. | ROS↑ dissociation of the Nrf2 – KEAP1 complex↑ Activation of Nrf2↑ ROS↑ phosphorylation of PKC↑ Activation of Nrf2↑ | [78] |
 FOXO | It stimulates transcription of genes for antioxidant proteins located in different subcellular compartments, (mitochondria, peroxisomes and plasma) | ROS can modulate FOXO activity at multiple levels post-translational modifications of FOXO (e.g., phosphorylation and acetylation), interactions with co-regulators, changes in FOXO subcellular localization | [79] |
 HIF | In most cases, HIF promotes cell survival through transcriptional regulation of angiogenic factors and glycolytic enzymes HIF may induce apoptosis by increasing the expression of pro-apoptotic factors such as NOXA, BNIP3, and Nix | ROS↑ PI3K/Akt and p38 MAPK↑ S-nitrosylation of HIF↑ HIF↑ | [80] |
 P53 | P53 can directly activate pro-apoptotic Bcl-2 family members (Bax and Bak) with the Bcl-2 family, thereby inducing mitochondrial outer membrane permeability (MOMP) and apoptosis | ROS can regulate p53 function not only by direct oxidative modification, but also indirectly by ATM or p38 MARK | [81] |
Signalling transduction level | Â | Â | Â |
 PI3K/AKT | Act as anti-apoptotic pathway to a variety of stimuli such as radiation, hypoxia by phosphorylation and inactivation of pro-apoptotic proteins | ROS modifies PTPases and PTEN PI3K↑ ROS modifies PI3K and Akt PI3K and Akt↓ survival signaling↓ | [82] |
 MAPK(ASK1) | Under non-stress conditions, ASK1 activity is blocked when combined with Trx-1 | ROS↑ Trx-1 oxidation and release of ASK1↑ Activation of JNK and p38-MAPK↑ | [83] |
 AMPK |  AMPK acts as an energy sensing factor that links metabolism and maintains redox balance | AMP/ATP ratio↑ AMPK phosphorylation↑ ROS↑ AMPK↑(via S-glutamylation of cysteine on the α and β subunits of AMPK) | [48] |
Executive level | Â | Â | Â |
 FLIP | Bind to FADD ,caspase-8/10 and DR5 and form an AIC AIC prevents the formation of the DISC and activation of the caspase cascade | ROS↑ c-FLIP↓ cFLIP levels correlate with the proportion of different intracellular species of ROS, such as O2·- and H2O2 | |
 XIAP | Bind and inhibit caspases 3, 7 and 9 | H2O2↑ PI3K/Akt phosphorylation↓ link between XIAP and Akt↓ XIAP↓ | |
 Cytochrome c | Involve in oxidative phosphorylation and ATP production as a component of mitochondrial ETC | 1)ROS↑ intracellular Ca2+↑ nonspecific pores (MPT pores) ↑ OMMP↑ 2)ROS↑ the activation of Bcl-2 family (Bax and Bak) by regulating ASK1/JNK pathway OMMP↑ | |
 caspase9 and Apaf-1 | Apaf-1 and caspase 9 together with cytochrome c form a complex (apoptosome) | ROS (H2O2)↑ caspase-9 activation↑ | |
 Alox5 | Under caspase-9-deficient condition, Erk1-Alox5 is a potentially important signaling pathway to execute both apoptotic and nonapoptotic forms of cell death | ROS↑ Alox5-mediated lipid peroxidation↑ nuclear entry of cell death-inducing molecules EndoG and TIA-1↑ | [93] |