Untitled

Funder

Organizational Unit

Publications

Exploring the contribution of mitochondrial dynamics to multiple acyl-CoA dehydrogenase deficiency-related phenotype

Publication . Brandão, Sofia R.; Ferreira, Rita; Rocha, Hugo

Mitochondrial fatty acid β-oxidation disorders (FAOD) are among the diseases detected by newborn screening in most developed countries. Alterations of mitochondrial functionality are characteristic of these metabolic disorders. However, many questions remain to be clarified, namely how the interplay between the signaling pathways harbored in mitochondria contributes to the disease-related phenotype. Herein, we overview the role of mitochondria on the regulation of cell homeostasis through the production of ROS, mitophagy, apoptosis, and mitochondrial biogenesis. Emphasis is given to the signaling pathways involving MnSOD, sirtuins and PGC-1α, which seem to contribute to FAOD phenotype, namely to multiple acyl-CoA dehydrogenase deficiency (MADD). The association between phenotype and genotype is not straightforward, suggesting that specific molecular mechanisms may contribute to MADD pathogenesis, making MADD an interesting model to better understand this interplay. However, more work needs to be done envisioning the development of novel therapeutic strategies.

2019-06-19Journal article

Restricted access

Use of MALDI-TOF Mass Spectrometry to Assay the Transthyretin V30M Mutation in Serum From a Liver Transplant Donor

Publication . Lacerda, Pedro C.; Moreira, Luciana; Vitorino, Rui; Costa, Paulo P.

Familial amyloidotic polyneuropathy (FAP), Portuguese type, or ATTR V30M is an autosomal dominant inherited disorder caused by a mutation in the transthyretin gene, with a valine/methionine substitution at position 30 (TTRV30M). ATTRV30Mis characterized by a progressive sensory/autonomic polyneuropathy and multiple organ dysfunction. Liver transplantation is the main therapeutic option,as it virtually eliminates the production of circulating TTR V30M, which occurs predominantly in the liver.

2015-05Journal article

Restricted access

Insight into the molecular basis of Schistosoma haematobium-induced bladder cancer through urine proteomics

Publication . Bernardo, Carina; Cunha, Maria Cláudia; Santos, Júlio Henrique; da Costa, José M Correia; Brindley, Paul J; Lopes, Carlos; Amado, Francisco; Ferreira, Rita; Vitorino, Rui; Santos, Lúcio Lara

Infection due to Schistosoma haematobium is carcinogenic. However, the cellular and molecular mechanisms underlying urogenital schistosomiasis (UGS)-induced carcinogenesis have not been well defined. Conceptually, early molecular detection of this phenomenon, through non-invasive procedures, seems feasible and is desirable. Previous analysis of urine collected during UGS suggests that estrogen metabolites, including depurinating adducts, may be useful for this purpose. Here, a new direction was pursued: the identification of molecular pathways and potential biomarkers in S. haematobium-induced bladder cancer by analyzing the proteome profiling of urine samples from UGS patients. GeLC-MS/MS followed by protein-protein interaction analysis indicated oxidative stress and immune defense systems responsible for microbicide activity are the most representative clusters in UGS patients. Proteins involved in immunity, negative regulation of endopeptidase activity, and inflammation were more prevalent in UGS patients with bladder cancer, whereas proteins with roles in renal system process, sensory perception, and gas and oxygen transport were more abundant in subjects with urothelial carcinoma not associated with UGS. These findings highlighted a Th2-type immune response induced by S. haematobium, which seems to be further modulated by tumorigenesis, resulting in high-grade bladder cancer characterized by an inflammatory response and complement activation alternative pathway. These findings established a starting point for the development of multimarker strategies for the early detection of UGS-induced bladder cancer.

2016-08Journal article

Restricted access