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Photobiomodulation Therapy in Orthopedics
Published in Kohlstadt Ingrid, Cintron Kenneth, Metabolic Therapies in Orthopedics, Second Edition, 2018
It is possible that blue light interacts with mitochondrial chromophores in the same way as red/NIR light since heme centers that are widespread in cytochromes have a significant absorption peak that coincides with the Soret band of porphyrins. However, there are several other plausible chromophores for blue light (and to a lesser extent green light). It should be noted that the term “blue light” can refer to a relatively wide range of wavelengths such as violet (390–425 nm), indigo (425–450 nm), royal blue (450–475 nm), blue green (475–500 nm). Because of the width of a typical absorption band (30 nm full width half maximum), it is theoretically possible that blue light could be absorbed by several distinct chromophores. For blue light these potential chromophores are in order of increasing wavelength: (A) tryptophan that can be photo-oxidized to form 6-formylindolo[3,2-b]carbazole (FICZ) that acts as an endogenous ligand of the aryl-hydrocarbon receptor (AhR) [30, 31]. The shortest wavelength blue light (380–400 nm) would be optimal here, as in general UV wavelengths are thought to be responsible for trytptophan photodegradation. (B) Next is the Soret band of heme groups (400 nm) where presumably similar processes are initiated as have been proposed for red/NIR light. Cytochromes b and a/a(3) were found to be responsible for the inhibitory effects of blue light on yeast [32]. (C) Wavelengths in the 440 nm range have been found to be optimal for activation of cryptochromes [33]. Cryptochromes are blue-light sensitive flavoproteins that have wide applications in plants and lower life-forms, mediating such functions as photomorphogenesis [34]. Cryptochromes are thought to play a role in entraining circadian rhythms [35] and may even be involved in sensing of magnetic fields in fruit flies [36]. Cryptochromes have recently been found to be expressed in some mammalian cells and tissues [37] and also to have activity in regulating circadian rhythms [38]. (D) The family of opsins are light-sensitive G-protein coupled receptors that rely on isomerization of cis-retinal. The wavelength maximum can range from UVA all the way to the green and red, but melanopsin (OPN4) has a λmax of 479 nm [39]. The signaling pathways differ between different opsins. Opsins signal via two main pathways depending on the type of G-protein they are coupled with [40, 41]. Those opsins (OPN1, OPN2, OPN3, OPN5) that are coupled with Go, Gi, Gt, Gs proteins, signal via a pathway involving cyclic nucleotides (cAMP and cGMP). On the other hand, OPN4 (melanopsin) is coupled to Gq and signals via the phospholipase C pathway leading to production of inositol triphosphate and di-acylglycerol. These signaling pathways are shown in Figure 6.2. It is known that activation of retinal opsins by blue light can generate ROS, which is partly responsible for ocular phototoxicity caused by violet and blue light [42].
Genetic identification of preoptic neurons that regulate body temperature in mice
Published in Temperature, 2022
Natalia L. S. Machado, Clifford B. Saper
Several clusters of glutamatergic neurons in the POA of mice that express EP3R also co-express QRFP [30], PACAP [21,23], BDNF [20], Esr1, the leptin receptor [14] and a violet-light-sensitive opsin (Opn5) [40] (for a more complete list of genetic markers expressed in EP3R-expressing POA neurons see Upton et al., 202133). This evidence suggests that EP3R-expressing MnPO neurons are a component of the MnPO glutamatergic population that causes a fall in Tb when activated. Hence, elevation of Tb would require that the EP3R would inhibit the MnPO hypothermic neurons during inflammatory conditions to generate fever. As Vglut2-expressing MnPO neurons project directly to the DHA/DMH and the RPa in mice [24,41], we have proposed a model where MnPOVglut hypothermic neurons contact inhibitory interneurons in the DHA/DMH or RPa to produce hypothermia and mediate fever(Figure. 2).
Therapeutic Nuclear Magnetic Resonance affects the core clock mechanism and associated Hypoxia-inducible factor-1
Published in Chronobiology International, 2021
Viktoria Thöni, Regina Oliva, David Mauracher, Margit Egg
The circadian clock is intimately linked with the hypoxic signaling pathway. In zebrafish, we were able to show that the bidirectional link between both pathways exists at the molecular, physiological, and organismic level (Egg et al. 2013, 2014; Pelster and Egg 2015, 2018; Sandbichler et al. 2018). The same mutual interaction was subsequently found in mammals and, therefore, appears to represent a fundamental aspect of eukaryotic cell biology (Adamovich et al. 2016; Manella et al. 2020; Peek et al. 2016; Wu et al. 2016). In a first study on tNMR, we investigated its effects on the cellular clocks and the hypoxic signaling pathway in zebrafish (Oliva et al. 2018). We used a tNMR dose of a single hour repeated for four consecutive days (4 h in total) on zebrafish cells and larvae, but found only minor effects (Oliva et al. 2018). To exclude that a too short irradiation time might have been the reason, in the present study we extended the total irradiation time to 6 h or 12 h, respectively. Additionally, we compared fibroblast cell lines of two different model organisms, the zebrafish fibroblast cell line Z3 and the mouse fibroblast cell line NIH3-T3. Apart from the teleost genome duplication, which occurred in fish and led to a higher number of clock gene isoforms compared to mammals (Pelster and Egg 2018), the circadian clock of both organisms also shows functional differences. Fish cells can be directly entrained to light-dark cycles (Froland Steindal and Whitmore 2019), similar to the cells of Drosophila. In zebrafish, the photosensitivity of cells was shown to depend on the expression of melanopsin (OPN4), which belongs to the protein family of the nonvisual opsins (Sousa et al. 2017). Due to the lack of OPN4 expression in mammalian peripheral clocks, they commonly do not respond directly to an external change of light (Froland Steindal and Whitmore 2019). However, direct light responsiveness was recently found in human adipocytes, which were shown to express OPN4 as well (Ondrusova et al. 2017), as it was in mouse skin cells, which express OPN5 (Buhr et al. 2019). In addition, we compared the effects of tNMR with those of direct light irradiation and with those of the glucocorticoid dexamethasone (DEX). DEX is known to synchronize the cellular clocks of zebrafish cells (Sousa et al. 2017), as well as those of mouse cells (Balsalobre et al. 2000; Chen et al. 2017; Nagoshi et al. 2004; So et al. 2009).