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Connexin43 promotes exocytosis of damaged lysosomes through actin remodelling

Domingues, Neuza S.; Catarino, Steve; Cristóvão, Beatriz; Rodrigues, Lisa; Carvalho, Filomena A; Sarmento, Maria João; Zuzarte, Mónica

A robust and efficient cellular response to lysosomal membrane damage prevents leakage from the lysosome lumen into the cytoplasm. This response is understood to happen through either lysosomal membrane repair or lysophagy. Here we report exocytosis as a third response mechanism to lysosomal damage, which is further potentiated when membrane repair or lysosomal degradation mechanisms are impaired. We show that ...


Unveiling the antitumor mechanism of 7α-acetoxy-6β-hydroxyroyleanone from Plect...

Magalhães, Mariana; Domínguez-Martín, Eva María; Jorge, Joana; Gonçalves, Ana Cristina; Massenzio, Francesca; Spigarelli, Renato

Glioblastoma (GB) is the most aggressive and prevalent glioma within the central nervous system. Despite considerable efforts, GB continues to exhibit a dismal 5-year survival rate (∼6%). This is largely attributed to unfavorable prognosis and lack of viable treatment options. Therefore, novel therapies centered around plant-derived compounds emerge as a compelling avenue to enhance patient survival and well-be...


Effect of blueberry supplementation on a diet-induced rat model of prediabetes—...

Ferreira, Gonçalo; Vieira, Pedro; Alves, André; Nunes, Sara; Preguiça, Inês; Martins-Marques, Tânia; Ribeiro, Tânia; Girão, Henrique; Figueirinha, Artur

Blueberries, red fruits enriched in polyphenols and fibers, are envisaged as a promising nutraceutical intervention in a plethora of metabolic diseases. Prediabetes, an intermediate state between normal glucose tolerance and type 2 diabetes, fuels the development of complications, including hepatic steatosis. In previous work, we have demonstrated that blueberry juice (BJ) supplementation benefits glycemic cont...


Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endos...

Hernandez-Perez, Ines; Rubio, Javier; Baumann, Adrian; Girão, Henrique; Ferrando, Miriam; Rebollo, Elena; Aragay, Anna M; Geli, María Isabel

Kazrin is a protein widely expressed in vertebrates whose depletion causes a myriad of developmental defects, in part derived from altered cell adhesion and migration, as well as failure to undergo epidermal to mesenchymal transition. However, the primary molecular role of kazrin, which might contribute to all these functions, has not been elucidated yet. We previously identified one of its isoforms, kazrin C, ...


Alvespimycin Inhibits Heat Shock Protein 90 and Overcomes Imatinib Resistance i...

Alves, Raquel; Santos, Diogo; Jorge, Joana; Gonçalves, Ana Cristina; Catarino, Steve; Girão, Henrique; Melo, Joana Barbosa; Sarmento-Ribeiro, Ana Bela

Heat shock protein 90 (HSP90) facilitates folding and stability and prevents the degradation of multiple client proteins. One of these HSP90 clients is BCR-ABL, the oncoprotein characteristic of chronic myeloid leukemia (CML) and the target of tyrosine kinase inhibitors, such as imatinib. Alvespimycin is an HSP90 inhibitor with better pharmacokinetic properties and fewer side effects than other similar drugs, b...


Cx43-mediated hyphal folding counteracts phagosome integrity loss during fungal...

Cristóvão, Beatriz; Rodrigues, Lisa; Catarino, Steve; Abreu, Mónica; Gonçalves, Teresa; Domingues, Neuza S.; Girão, Henrique

Phagolysosomes are crucial organelles during the elimination of pathogens by host cells. The maintenance of their membrane integrity is vital during stressful conditions, such as during Candida albicans infection. As the fungal hyphae grow, the phagolysosome membrane expands to ensure that the growing fungus remains entrapped. Additionally, actin structures surrounding the hyphae-containing phagosome were recen...


Aromatic Plant-Based Functional Foods: A Natural Approach to Manage Cardiovascu...

Zuzarte, Mónica; Girão, Henrique; Salgueiro, Lígia

Aromatic plants and their essential oils have shown beneficial effects on the cardiovascular system and, therefore, are potential raw materials in the development of functional foods. However, despite their undeniable potential, essential oils present several limitations that need to be addressed, such as stability, poor solubility, undesirable sensory effects, and low bioavailability. The present review provid...



MYOC Gene Sequencing Analysis in Primary Open-Angle Glaucoma Patients from the ...

Silva, Filipe; Ferreira, Filipa; Faria, Pedro; Sobral, Isa; Rodrigues, Mariana; Pratas, João; Silva, Filipe; Grazina, Manuela; Moura Pereira, José

Primary open-angle glaucoma is the most frequent subtype of glaucoma. Relatives of primary open-angle glaucoma patients have an increased risk of developing the disease, suggesting a genetic predisposition to the disease. MYOC was the first primary open-angle glaucoma-causing gene identified. This study aimed to identify sequence variations in the MYOC gene that may be responsible for the phenotype in a group o...



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