Photodynamic Physiology—Photonanomanipulations in Cellular Physiology with Protein Photosensitizers

Jiang, Haowei; Li, Yuan; Cui, Zong Jie

doi:10.3389/fphys.2017.00191

Cited by 26 publications

(31 citation statements)

References 138 publications

(231 reference statements)

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“…Consequently, such compounds exhibit a certain toxicity to other, healthy tissues 18,19 . Alternatively, the use of proteins as genetically encoded 1 O 2 generators offers new ways of designing, synthesizing, and targeting of biomacromolecules containing PS 20 .…”

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confidence: 99%

“…Recently, significant efforts have been invested into the design of protein PSs containing FMN due to its high value of Φ Δ 15, [21][22][23] . On the other hand, genetically encoded fluorescent tags have inherently very low efficiency of 1 O 2 production (Φ Δ < 0.09) 15,20,24,25 . These observations point to a strong effect of the surrounding protein matrix on 1 O 2 production efficiency by the chromophore 21 .…”

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confidence: 99%

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Photoinduced damage of AsLOV2 domain is accompanied by increased singlet oxygen production due to flavin dissociation

Petrenčáková

Filandr

Hovan

et al. 2020

Sci Rep

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Flavin mononucleotide (FMN) belongs to the group of very efficient endogenous photosensitizers producing singlet oxygen, 1 o 2 , but with limited ability to be targeted. On the other hand, in geneticallyencoded photosensitizers, which can be targeted by means of various tags, the efficiency of FMN to produce 1 o 2 is significantly diminished due to its interactions with surrounding amino acid residues. Recently, an increase of 1 o 2 production yield by FMN buried in a protein matrix was achieved by a decrease of quenching of the cofactor excited states by weakening of the protein-FMN interactions while still forming a complex. Here, we suggest an alternative approach which relies on the blue light irradiation-induced dissociation of FMN to solvent. This dissociation unlocks the full capacity of FMN as 1 o 2 producer. Our suggestion is based on the study of an irradiation effect on two variants of the LOV2 domain from Avena sativa; wild type, AsLOV2 wt, and the variant with a replaced cysteine residue, AsLOV2 C450A. We detected irradiation-induced conformational changes as well as oxidation of several amino acids in both AsLOV2 variants. Detailed analysis of these observations indicates that irradiationinduced increase in 1 o 2 production is caused by a release of FMN from the protein. Moreover, an increased FMN dissociation from AsLOV2 wt in comparison with AsLOV2 C450A points to a role of C450 oxidation in repelling the cofactor from the protein. Flavin mononucleotide (FMN) belongs to a group of efficient endogenous photosensitizers in cells with rather high singlet oxygen, 1 O 2 , quantum yield (Φ Δ) within the range 0.51-0.65 1,2. Depending on FMN concentrations and concentrations of available oxygen, the flavin(s) can be even more effective 1 O 2 generators than exogenous porphyrins used for cell killing in photodynamic therapy (PDT). To minimize the potential deleterious effect of flavins to cells, the isoalloxazine moiety of flavin cofactors is typically deeply buried in the protein core of flavoenzymes 3 or storage proteins 4. Singlet oxygen, the lowest energy excited electronic state of molecular oxygen, belongs to the group of reactive oxygen species (ROS), which includes superoxide anion (O 2 •−), hydrogen peroxide (H 2 O 2), and hydroxyl radical (HO •), enabling to oxidize and/or oxygenate many biologically relevant molecules 5,6. Singlet oxygen can be produced in a variety of ways by physical mechanisms, including energy transfer from the excited triplet states of particular chromophores to molecular oxygen 7 , or by chemical mechanisms as one of the products of peroxidase enzymes 8. In biological systems, 1 O 2 is usually generated by electronic energy transfer from an excited state of a photosensitive molecule, so-called photosensitizer (PS), to ground state O 2 6. The high reactivity of singlet oxygen towards biological molecules is relevant in the context of PDT 9 and chromophore-assisted laser inactivation (CALI) of proteins and cells 10,11 .

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confidence: 99%

mentioning

confidence: 99%

Photoinduced damage of AsLOV2 domain is accompanied by increased singlet oxygen production due to flavin dissociation

Petrenčáková

Filandr

Hovan

et al. 2020

Sci Rep

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“…Met, Cys, His, Trp, and Tyr residues are ready oxidative targets for 1 O 2 generated in type II photodynamic actions [32,62,63]. Met oxidation is especially known to modulate protein activities and related cellular functions [64].…”

Section: Discussionmentioning

confidence: 99%

“…Met oxidation is especially known to modulate protein activities and related cellular functions [64]. CCK1R is the first reported G-protein-coupled receptor to be permanently activated by 1 O 2 generated in photodynamic action with photosensitizers SALPC, KillerRed, and miniSOG [32,41,42]. Although every detail of the molecular mechanisms and oxidant chemical bases for such permanent activation are not yet known, a comparison of residues key to the activation of CCK1R and CCK2R (but also susceptible to 1 O 2 oxidation) might give some useful hints.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, it has recently been found that the CCK1 receptor (CCK1R) could be readily activated by the lowest-lying excited state of molecular oxygen (i.e., the delta singlet oxygen, 1 O 2 ) in the complete absence of any agonist, as described below. 1 O 2 is typically generated in a type II photodynamic action after photosensitizer absorption of a photon at an appropriate wavelength [31,32]. One widely used class of chemical photosensitizers is phthalocyanines (Pc) [33].…”

Section: Introductionmentioning

confidence: 99%

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Permanent Photodynamic Activation of the Cholecystokinin 2 Receptor

Tang

Cui

2020

Biomolecules

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The cholecystokinin 2 receptor (CCK2R) is expressed in the central nervous system and peripheral tissues, playing an important role in higher nervous and gastrointestinal functions, pain sensation, and cancer growth. CCK2R is reversibly activated by cholecystokinin or gastrin, but whether it can be activated permanently is not known. In this work, we found that CCK2R expressed ectopically in CHO-K1 cells was permanently activated in the dark by sulfonated aluminum phthalocyanine (SALPC/AlPcS4, 10–1000 nM), as monitored by Fura-2 fluorescent calcium imaging. Permanent CCK2R activation was also observed with AlPcS2, but not PcS4. CCK2R previously exposed to SALPC (3 and 10 nM) was sensitized by subsequent light irradiation (>580 nm, 31.5 mW·cm−2). After the genetically encoded protein photosensitizer mini singlet oxygen generator (miniSOG) was fused to the N-terminus of CCK2R and expressed in CHO-K1 cells, light irradiation (450 nm, 85 mW·cm−2) activated in-frame CCK2R (miniSOG-CCK2R), permanently triggering persistent calcium oscillations blocked by the CCK2R antagonist YM 022 (30 nM). From these data, it is concluded that SALPC is a long-lasting CCK2R agonist in the dark, and CCK2R is photogenetically activated permanently with miniSOG as photosensitizer. These properties of SALPC and CCK2R could be used to study CCK2R physiology and possibly for pain and cancer therapies.

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A Genetically Encoded RNA Photosensitizer for Targeted Cell Regulation

Keshri

Sun

et al. 2020

Angewandte Chemie

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Genetically encoded RNA devices have emerged for various cellular applications in imaging and biosensing, but their functions as precise regulators in living systems are still limited. Inspired by protein photosensitizers, we propose here a genetically encoded RNA aptamer based photosensitizer (GRAP). Upon illumination, the RNA photosensitizer can controllably generate reactive oxygen species for targeted cell regulation. The GRAP system can be selectively activated by endogenous stimuli and light of different wavelengths. Compared with their protein analogues, GRAP is highly programmable and exhibits reduced off-target effects. These results indicate that GRAP enables efficient noninvasive target cell ablation with high temporal and spatial precision. This new RNA regulator system will be widely used for optogenetics, targeted cell ablation, subcellular manipulation, and imaging.

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Photodynamic Physiology—Photonanomanipulations in Cellular Physiology with Protein Photosensitizers

Cited by 26 publications

References 138 publications

Photoinduced damage of AsLOV2 domain is accompanied by increased singlet oxygen production due to flavin dissociation

Photoinduced damage of AsLOV2 domain is accompanied by increased singlet oxygen production due to flavin dissociation

Permanent Photodynamic Activation of the Cholecystokinin 2 Receptor

A Genetically Encoded RNA Photosensitizer for Targeted Cell Regulation

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