title: Photooxidation of Tryptophan and Tyrosine Residues in Human Serum Albumin Sensitized by Pterin: A Model for Globular Protein Photodamage in Skin.
abstract: Human serum albumin (HSA) is the most abundant protein in the circulatory system. Oxidized albumin was identified in the skin of patients suffering from vitiligo, a depigmentation disorder in which the protection against ultraviolet (UV) radiation fails because of the lack of melanin. Oxidized pterins, efficient photosensitizers under UV-A irradiation, accumulate in the skin affected by vitiligo. In this work, we have investigated the ability of pterin (Ptr), the parent compound of oxidized pterins, to induce structural and chemical changes in HSA under UV-A irradiation. Our results showed that Ptr is able to photoinduce oxidation of the protein in at least two amino acid residues: tryptophan (Trp) and tyrosine (Tyr). HSA undergoes oligomerization, yielding protein structures whose molecular weight increases with irradiation time. The protein cross-linking, due to the formation of dimers of Tyr, does not significantly affect the secondary and tertiary structures of HSA. Trp is consumed in the photosensitized process, and N-formylkynurenine was identified as one of its oxidation products. The photosensitization of HSA takes place via a purely dynamic process, which involves the triplet excited state of Ptr. The results presented in this work suggest that protein photodamage mediated by endogenous photosensitizers can significantly contribute to the harmful effects of UV-A radiation on the human skin.
authors: Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT La Plata-CONICET , Casilla de Correo 16, Sucursal 4, 1900 La Plata, Argentina.
authors: Lara O
authors: LO
authors: Reid
authors: Instituto de Química y Físico-Químicas Biológicas (IQUIFIB), Universidad de Buenos Aires , Junín 956, 1113 Buenos Aires, Argentina.
authors: Ernesto A
authors: EA
authors: Roman
authors: Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT La Plata-CONICET , Casilla de Correo 16, Sucursal 4, 1900 La Plata, Argentina.
authors: Andrés H
authors: AH
authors: Thomas
authors: Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT La Plata-CONICET , Casilla de Correo 16, Sucursal 4, 1900 La Plata, Argentina.
authors: M Laura
authors: ML
authors: Dántola
mesh_terms: D003432:Cross-Linking Reagents; D006801:Humans; D008956:Models, Chemical; D010084:Oxidation-Reduction; D055668:Photochemical Processes; D017319:Photosensitizing Agents / Q000737:chemistry / Q000528:radiation effects; D011622:Pterins / Q000737:chemistry / Q000528:radiation effects; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism / Q000528:radiation effects*; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D015595:Skin Aging / Q000528:radiation effects; D014364:Tryptophan / Q000737:chemistry / Q000528:radiation effects; D014443:Tyrosine / Q000737:chemistry / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D011622:Pterins; D012709:Serum Albumin; D014443:Tyrosine; D014364:Tryptophan