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Review
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The Influence of Light on Reactive Oxygen Species and NF-кB in Disease Progression

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Review

The Influence of Light on Reactive Oxygen Species and NF-кB in Disease Progression

Naresh Kumar Rajendran et al. Antioxidants (Basel).

Abstract

Reactive oxygen species (ROS) are important secondary metabolites that play major roles in signaling pathways, with their levels often used as analytical tools to investigate various cellular scenarios. They potentially damage genetic material and facilitate tumorigenesis by inhibiting certain tumor suppressors. In diabetic conditions, substantial levels of ROS stimulate oxidative stress through specialized precursors and enzymatic activity, while minimum levels are required for proper wound healing. Photobiomodulation (PBM) uses light to stimulate cellular mechanisms and facilitate the removal of oxidative stress. Photodynamic therapy (PDT) generates ROS to induce selective tumor destruction. The regulatory roles of PBM via crosstalk between ROS and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) are substantial for the appropriate management of various conditions.

Keywords: cancer; diabetes; nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB); photobiomodulation; reactive oxygen species (ROS); wound healing.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Free radical generation. Free radicals formed by the electron transport chain are immediately removed and converted to water through a series of enzymatic reactions. ETC: electron transport chain; SOD: superoxide dismutase; CAT: catalase; GPX: glutathione peroxidase; GR: glutathione reductase; PRX: peroxiredoxins; GSH: glutathione; GSSG: glutathione disulfide; Trx: thioredoxin; O2: superoxide; NO•: nitric oxide; ONOO: peroxynitrite; H2O2: hydrogen peroxide.
Figure 2
Figure 2
During photodynamic therapy (PDT), generated reactive oxygen species (ROS) kill the targeted tumor cells. PDT depends on the successful accumulation of photosensitizers (PSs) in tumor cells to initiate the process of irradiation of targeted areas for activation of the PSs. When irradiated with light of a specific wavelength, a photochemical reaction leads to the production of ROS in the presence of oxygen. When the PS absorbs the photon energy it is excited and jumps from the ground state to the excited singlet state and the energy is emitted back as fluorescence or heat via internal conversion. Should intersystem-crossing occur, the PS is converted to an excited triplet state, which can transfer electrons with cellular biomolecules, ultimately leading to the generation of ROS in a Type I reaction. Alternatively, the excited triplet state PS transfers its electrons to ground triplet state molecular oxygen (3O2), leading to the generation of an excited singlet oxygen (1O2) in a Type II reaction.
Figure 3
Figure 3
Mechanism of photobiomodulation (PBM). When low-powered light (LILI) enters the cell, it is immediately absorbed by cytochrome c oxidase, which is present in mitochondria. This results in an increased respiratory chain reaction and the overall redox reaction is altered. The increase in reactive oxygen species (ROS) stimulates the oxidation of cysteine molecules. The glutathionylation of IkB and S-glutathionylation of p50 activates NF-kB and transcription of specific genes. This further stimulates the activation of the IkB kinase complex, leading to phosphorylation, ubiquitination, and degradation of IkB proteins. Released NF-kB dimers then translocate into the nucleus, bind to specific DNA sequences, and promote the transcription of target genes such as interleukin (IL)-2, IL-6, IL-8, inducible nitric oxide synthase (iNOS), COX-2, and matrix metallopeptidases (MMP)-9.
Figure 4
Figure 4
Activation of NF-кB by the canonical and/or the noncanonical pathway. The canonical NF- кB-activating pathway depends on the phosphorylation of IкB-kinase (IKK) β. The phosphorylation and ubiquitination of IкBα translocate NF-кB into the nucleus. where it helps in the transcription of target genes. Many membrane-bound ligands involved in activating the NF-кB pathway act as effective upstream regulators and the IKK complex is the common upstream component of all NF-кB pathways. In contrast, the non-canonical pathway is NF-kB essential modulator (NEMO)-independent and depends on IKKα activation to induce the NF-kB/RelB activation complex, leading to the phosphorylation of p100 and the generation of p52/RelB complexes.
Figure 5
Figure 5
NF-κB activation in the progression of cancer by regulating genes involved in tumor cell proliferation, cell growth, survival, angiogenesis, tumor promotion, and metastasis. BCL2: B-cell lymphoma protein 2; BCL-XL, also known as BCL2-like 1; BFL1, also known as BCL2A1; CDK2: cyclin-dependent kinase 2; COX2: cyclooxygenase 2; CXCL: chemokine (C-X-C motif) ligand; DR: death receptor; ELAM1: endothelial adhesion molecule 1; FLIP, also known as CASP8; GADD45beta: growth arrest and DNA-damage-inducible protein beta; HIF1alpha: hypoxia-inducible factor 1 alpha; ICAM1: intracellular adhesion molecule 1; IEX-1L: radiation-inducible immediate early gene (also known as IER3); IL: interleukin; iNOS: inducible nitric oxide synthase; KAL1: Kallmann syndrome 1 sequence; MCP1: monocyte chemoattractant protein 1 (also known as CCL2); MIP2: macrophage inflammatory protein 2; MMP: matrix metalloproteinase; MnSOD: manganese superoxide dismutase (also known as SOD2); TNF: tumor necrosis factor; TRAF: TNF receptor-associated factor; uPA: urokinase plasminogen activator; VCAM1: vascular cell adhesion molecule 1; VEGF: vascular endothelial growth factor; XIAP: X-linked inhibitor of apoptosis protein.
Figure 6
Figure 6
Role and activation of NF-кB in diabetes mellitus. NF-кB regulates the expression of cytokine-induced genes that affect pro- or anti-apoptotic cascades. NF-кB is one of the major causes in the development of insulin resistance. Tumor necrosis factor (TNF) predominantly induces insulin resistance by the serine phosphorylation of insulin receptor substrate-1 (IRS1), and NF-кB is a major cause of insulin resistance.

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