Photosensitization in porphyrias and photodynamic therapy involves TRPA1 and TRPV1

Babes, AlexandruFriedrich-Alexander University Erlangen-Nürnberg,University of Bucharest (författare)

Photosensitization, an exaggerated sensitivity to harmless light, occurs genetically in rare diseases, such as porphyrias, and in photodynamic therapy where short-term toxicity is intended. A common feature is the experience of pain from bright light. In human subjects, skin exposure to 405 nm light induced moderate pain, which was intensified by pretreatment with aminolevulinic acid. In heterologous expression systems and cultured sensory neurons, exposure to blue light activated TRPA1 and, to a lesser extent, TRPV1 channels in the absence of additional photosensitization. Pretreatment with aminolevulinic acid or with protoporphyrin IX dramatically increased the light sensitivity of both TRPA1 and TRPV1 via generation of reactive oxygen species. Artificial lipid bilayers equipped with purified human TRPA1 showed substantial single-channel activity only in the presence of protoporphyrin IX and blue light. Photosensitivity and photosensitization could be demonstrated in freshly isolated mouse tissues and led to TRP channel-dependent release of proinflammatory neuropeptides upon illumination. With antagonists in clinical development, these findings may help to alleviate pain during photodynamic therapy and also allow for disease modification in porphyria patients.

Sauer, Susanne K.Friedrich-Alexander University Erlangen-Nürnberg (författare)
Moparthi, LavanyaLund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)bioc-lmi (författare)
Kichko, Tatjana I.Friedrich-Alexander University Erlangen-Nürnberg (författare)
Neacsu, CristianFriedrich-Alexander University Erlangen-Nürnberg (författare)
Namer, BarbaraFriedrich-Alexander University Erlangen-Nürnberg (författare)
Filipovic, MilosFriedrich-Alexander University Erlangen-Nürnberg (författare)
Zygmunt, Peter M.Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kfar-pzy (författare)
Reeh, Peter W.Friedrich-Alexander University Erlangen-Nürnberg (författare)
Fischer, Michael J MFriedrich-Alexander University Erlangen-Nürnberg (författare)
Friedrich-Alexander University Erlangen-NürnbergUniversity of Bucharest (creator_code:org_t)

Av författaren/redakt...: Babes, Alexandru; Sauer, Susanne K ...; Moparthi, Lavany ...; Kichko, Tatjana ...; Neacsu, Cristian; Namer, Barbara; visa fler...; Filipovic, Milos; Zygmunt, Peter M ...; Reeh, Peter W.; Fischer, Michael ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Neurologi

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