Browsing by Subject "Cathepsin D"
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- PublicationRestrictedDiagnosis of vitality in skin wounds in the ligature marks resulting from suicide hanging(Lippincott, Williams & Wilkins, 2017-09) Giménez, M.; Martínez Díaz, F.; Pérez Cárceles, María Dolores; Osuna, E.; Nuno Vieira, D.; Luna, Aurelio; Falcón Romero, María; Legaz Pérez, Isabel; Ciencias SociosanitariasAscertaining the vital origin of skin wounds is one of the most challenging problems in forensic pathology. The forensic literature describes biomarkers and methods for differentiating vital and postmortem wounds, although no clear conclusions have been reached. The aim of this study was to characterize human vital wounds by analyzing the concentrations of metallic ions and the expression of P-selectin and cathepsin D in skin wounds in the ligature marks in a cohort of suicidal hangings for which vitality was previously demonstrated. A total of 71 skin wounds were analyzed within a postmortem interval of 19 to 36 hours. The concentration of Fe, Zn, Mg, and Ca and the expression of P-selectin and cathepsin D were analyzed together and separately. The majority of autopsied suicidal hangings were men (86%) with complete hanging mode (60.7%) in which there was a high frequency of subcutaneous injuries (78.3%). High concentrations of Ca and Mg compared with Fe and Zn were found. Ca and Zn concentrations decreased, and Fe concentration increased with the seriousness of the injury. A high percentage of moderately negative expression of both proteins was correlated with subcutaneous injury and low or medium concentrations of Fe. In conclusion, the joint study of metallic ions and proteins allows to characterize and to differentiate an injured vital wound of noninjured skin, especially when the damage in the tissue affects to the majority of the structures of the skin, but these results will need to be complemented with other biomarkers in time-controlled samples to further help in the differentiation of vital and postmortem wounds.
- PublicationRestrictedImmunohistochemistry as a tool to characterize human skin wounds of hanging marks(Romanian Society of Legal Medicine, 2019-03) Pérez Cárceles, María Dolores; Giménez, M.; Martínez Díaz, F.; Osuna, Eduardo; Luna, Aurelio; Legaz Pérez, Isabel; Ciencias SociosanitariasEstimation of age and vitality of human skin wounds both in the living and dead is essential in forensic practice. The use of immunohistochemical parameters for the age estimation and vitality of human skin wounds remains difficult. Forensic literature describes different biomarkers and methods for the differential diagnosis of vital and post-mortem wounds, but to this day it is unclear its utility. The aim of this study was analysed wounds vital origin in a series of suicidal hangings were vitality had been demonstrated using fibronectin, cathepsin D and P-selectin, in order to discover the morphological changes that occur in a vital wound, and consequently, find useful vital injury diagnosis markers. A total of 15 human vital skin wounds from ligature marks from deaths by suicidal hanging and skin controls from same cadaver were analyzed in a postmortem interval between 19-36 hours. Fibronectine, cathepsin D and P-selectin were detected by immunohistochemistry. Our result shows a strongly fibronectin-positive reaction in basement membranes and interstitial connective tissue in all specimen of wounds of ligature mark. Granular staining pattern characteristic of cathepsin D was observed mainly in the basal layer of the epidermis in normal and wound skin. Cathepsin D analysis in ligature mark showed moderate positive and strong positive cells. A weak positive immunoreactivity P-selectin were found in vital wound compared with undamaged skin. In conclusion, our data show an increase of fibronectin and cathepsin D immunoreactivity expression and a decrease of P-selectin immunoreactivity in skin wounds from ligature marks from deaths by suicidal hanging of a postmortem interval between 19-36 hours.
- PublicationOpen AccessMolecular insights into the interaction of cathepsin D and iron in chronic wound healing: exploring therapeutic potential and mechanisms(MDPI, 2025-02-21) Rodríguez-Moreno, María; Legaz Pérez, Isabel; Ciencias Sociosanitarias; Facultad de QuímicaBackground: Chronic wounds, such as diabetic ulcers, often fail to progress through healing due to persistent inflammation, infections, and extracellular matrix (ECM) imbalances. Cathepsin D, an aspartate protease active in acidic environments, plays a pivotal role in wound healing by mediating inflammatory responses, ECM remodeling, and macrophage phenotype transitions. Its dysregulation, however, can impair healing, highlighting the need for targeted modulation of its activity. The aim of this study was to investigate the molecular interaction between Fe2+ and cathepsin D’s catalytic core and ionic zipper under physiological and acidic conditions to identify strategies to enhance tissue repair and accelerate the healing of chronic wounds. Methods: The molecular structure of active cathepsin D was obtained from the Protein Data Bank (PDB) and analyzed using UCSF Chimera. Molecular interactions between cathepsin D and ferrous ions (Fe2+) were studied, focusing on key residues (D33 and D231) and ionic zipper residues (E5, E180, and D187). Results: Our results showed that the active form of cathepsin D, a 96 kDa dimer, consisted of heterodimers with distinct amino acid chains, where residues D33 and D231 formed the active site, and E5, E180, and D187 constituted the ionic zipper. A functional pocket containing the conserved residues D33 and D231, essential for proteolytic activity, was identified. At physiological pH (~7.5), D33 exhibited the most potent interactions with Fe2+, with interaction energies of −7 × 1017 J at oxygen atoms of the carboxylate group (OD1) and α-carbon (CA) atoms, whereas D231 showed slightly lower energies of −6 × 1017 J at γ-carbon atom (CG) and CA atoms. At acidic pH (~4), E5 was the primary interacting residue, with the shortest distance to Fe2+ (2.69 Å), and showed stable interactions across several atoms, emphasizing its role in metal binding. Conclusions: pH conditions strongly influence the interaction of cathepsin D with Fe2. At physiological pH, residues D33 and D231 demonstrate robust and energetically efficient binding with Fe2+. At the same time, under acidic conditions, E5 emerges as the primary residue involved, potentially affecting the ionic zipper of cathepsin D. These insights provide a molecular foundation for targeting specific residues to modulate cathepsin D activity, presenting promising opportunities for therapeutic strategies aimed at improving chronic wound healing.
- PublicationOpen AccessSignificance of the tumor protease cathepsin D for the biology of breast cancer(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Dian, Darius; Heublein, Sabine; Wiest, Irmi; Barthell, Lisa; Friese, Klaus; Jeschke, UdoCathepsin D is a protease involved in the metastasis and angiogenesis of mammary carcinomas. This review analyzes the significance of the tumor protease cathepsin D in mammary carcinomas as a tumor marker. We present a systematic overview based on a selective Medline search. Cathepsin D is expressed in mammary carcinomas and exhibits higher expression in invasive ductal carcinomas compared with lobular carcinomas. Nodal positive carcinomas showed reduced cathepsin D expression compared to lymph node metastases, and increased expression has been observed in hormone-receptor negative tumors. Thus, the expression of cathepsin varies between the two histological types. Increased cathepsin D expression in acinar affection has also been described. The lack of an association of cathepsin D with known prognostic factors such as CA15-3, ERalpha and ERbeta does not prevent it from being used as a tumor marker. Cathepsin has already been used along with other genes as a prognostic parameter for carcinoma patients in gene arrays. Histol Histopathol 29, 433-438 (2014)