Photoactivation of Hypericin Generates Singlet Oxygen in Mitochondria and Inhibits Succinoxidase

Thomas, Carin; MacGill, Randall S.; Miller, Glenn C.; Pardini, Ronald S.

doi:10.1111/j.1751-1097.1992.tb04208.x

Cited by 154 publications

(86 citation statements)

References 44 publications

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“…This indicates instability of the cytoplasmic membranes when associated with hypericin. Thomas et al (1992) have shown that through a process of singlet oxygen generation, photoactivation of hypericin inhibits succinoxidase activity of mitochondria isolated from bovine heart. The high affinity of hypericin for membranous cellular organelles suggests that hypericin may act also at the mitochondrial level in whole cells.…”

Section: Antiviral Activity Of Hypericin Against Hsv-1 87mentioning

confidence: 99%

The Antiviral Agent Hypericin hasin vitroActivity against HSV-1 Through Non-Specific Association with Viral and Cellular Membranes

Weber

Murray

North

et al. 1994

Antivir Chem Chemother

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The antiviral and virucidal compound, hypericin, was studied regarding its activity and possible mechanism against herpes simplex virus (HSV-1). It was determined that hypericin caused slight inhibition of viral adsorption to and penetration of Vero cells. Additionally, yield reduction assays suggested that hypericin was most effective against HSV-1 as a virucidal agent rather than as an intracellular antiviral agent. Fluorescence microscopy revealed that hypericin initially associated with cytoplasmic membranes and that over the course of time it became concentrated in intracellular membranous regions, probably the Golgi apparatus or endoplasmic reticulum (ER). These concentration events failed to inhibit glycosylation of either viral or cellular proteins and were effectively blocked by compounds which inhibit endocytosis or membrane cycling between the ER and Golgi. Based on fluorescence studies, it was determined that hypericin had non-specific affinity for protein and higher affinity for detergent and lipid. The evidence suggested that strong, non-specific association with membranes, both viral and cellular, are probably the basis of hypericin's virucidal and antiviral activity.

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Section: Antiviral Activity Of Hypericin Against Hsv-1 87mentioning

confidence: 99%

The Antiviral Agent Hypericin hasin vitroActivity against HSV-1 Through Non-Specific Association with Viral and Cellular Membranes

Weber

Murray

North

et al. 1994

Antivir Chem Chemother

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“…[2][3][4][5][6][7][8][9][10][11] In addition, hypericin has attracted attention for its antidepressant activity. [12][13][14][15] The interaction of light with hypericin and hypericin-like chromophores is clearly of fundamental biological importance.…”

Section: Introductionmentioning

confidence: 99%

Structure and Energetics of Ground-State Hypericin: Comparison of Experiment and Theory

1998

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Calculations of the energies of the ground-state un-ionized tautomers of hypericin have been performed at the RMP2/6-31G(d) level of theory, using geometries obtained with the 3-21G basis set and Hartree−Fock wave functions. It is found that only the so-called normal form is likely to be populated at room temperature and that only two of the three possible double tautomers correspond to minima on the potential energy surface. The effect of continuum aqueous solvation on the tautomer energies is negligible. The O---O distances between which the proton is transferred are reported and are consistent with that required for an adiabatic proton transfer, i.e., ∼2.5 Å. All 156 vibrational frequencies are tabulated and may be viewed at www.msg.ameslab.gov. For example, the vibrations in the range 320−660 cm-1 are coupled with O---O vibrations. The vibrations that are most clearly O---O vibrations occur in the range 400−500 cm-1. Twisting of the backbone occurs in a wide range of frequencies, from 230 to 1150 cm-1, while the motion corresponding to an inversion of the (nonplanar) backbone occur at very low frequencies, 80−150 cm-1. The results of these calculations are discussed in terms of ground-state heterogeneity of hypericin that has been invoked to explain its spectra and excited-state kinetics. Disciplines Chemistry CommentsReprinted ( 24, 1997; In Final Form: December 10, 1997 Calculations of the energies of the ground-state un-ionized tautomers of hypericin have been performed at the RMP2/6-31G(d) level of theory, using geometries obtained with the 3-21G basis set and Hartree-Fock wave functions. It is found that only the so-called normal form is likely to be populated at room temperature and that only two of the three possible double tautomers correspond to minima on the potential energy surface. The effect of continuum aqueous solvation on the tautomer energies is negligible. The O---O distances between which the proton is transferred are reported and are consistent with that required for an adiabatic proton transfer, i.e., ∼2.5 Å. All 156 vibrational frequencies are tabulated and may be viewed at www.msg.ameslab-.gov. For example, the vibrations in the range 320-660 cm -1 are coupled with O---O vibrations. The vibrations that are most clearly O---O vibrations occur in the range 400-500 cm -1 . Twisting of the backbone occurs in a wide range of frequencies, from 230 to 1150 cm -1 , while the motion corresponding to an inversion of the (nonplanar) backbone occur at very low frequencies, 80-150 cm -1 . The results of these calculations are discussed in terms of ground-state heterogeneity of hypericin that has been invoked to explain its spectra and excited-state kinetics. IntroductionThe naturally occurring polycyclic quinone hypericin (Scheme 1) is of current interest because of its light-induced 1 antiviral (especially anti-HIV) and antitumor activity. [2][3][4][5][6][7][8][9][10][11] In addition, hypericin has attracted attention for its antidepressant activity. [12][13][14][15] The interaction of...

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“…For the majority of the photosensitizer drugs the mechanism of action is connected with Type I (production of radicals) and Type II (production of singlet oxygen) photodynamic processes. It has been shown that antiviral and antitumoral photo-activities of Hyp are oxygen dependent [5][6]. However, others and we have suggested "an alternative" origin for the photo-induced activity of Hyp.…”

Section: Introductionmentioning

confidence: 93%

Multispectral confocal fluorescence imaging: monitoring of intracellular distribution of PKC influenced by photoactive drug hypericin

Kočanová¹,

Mateášik²,

Chorvát³

et al. 2004

Laser Phys. Lett.

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The spectral imaging with confocal microscopy was applied for evaluation of changes in sub-cellular distribution of protein kinase C (PKC) in glioblastoma cells after application of photosensitizer hypericin (Hyp). The distribution of PKC stained by fim-1-AM probe in presence of Hyp was determined by linear un-mixing algorithm from recorded spectral images. Comparison of the distribution of PKC in cells with and without Hyp indicates that presence of Hyp induces re-localization of PKC to the perinuclear area of cells. Moreover, linear co-localization pattern between distribution of Hyp and fim-1 indicates strong spatial overlapping of fim-1 and Hyp localization. This means that the re-localization of PKC in presence of Hyp could be the result of direct interaction between PKC and Hyp. It is shown, that spectral imaging and linear un-mixing is an approach that can enhance our ability to observe cellular structure and function by fluorescent probes even in the case of strong overlapping of their emission spectra with the spectra of photosensitizers.

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Photoactivation of Hypericin Generates Singlet Oxygen in Mitochondria and Inhibits Succinoxidase

Cited by 154 publications

References 44 publications

The Antiviral Agent Hypericin hasin vitroActivity against HSV-1 Through Non-Specific Association with Viral and Cellular Membranes

The Antiviral Agent Hypericin hasin vitroActivity against HSV-1 Through Non-Specific Association with Viral and Cellular Membranes

Structure and Energetics of Ground-State Hypericin: Comparison of Experiment and Theory

Multispectral confocal fluorescence imaging: monitoring of intracellular distribution of PKC influenced by photoactive drug hypericin

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