Browsing by Author "Fonseca, Ana Cláudia Rodrigues"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- Membrane permeability and aquaporin involvement in oxidative stress and cancerPublication . Fonseca, Ana Cláudia Rodrigues; Rodrigues, Maria da Graça Soveral, 1959-Aquaporins (AQPs) are a family of small transmembrane proteins present in all types of organisms and involved in the selective transport of water and small solutes such as glycerol in response to osmotic or solute gradients. So far, 13 isoforms were identified in humans and can be divided in three different groups according with their selectivity and sequence homology. AQPs were reported to be important in a wide range of physiological functions, such as water and energy homeostasis, exocrine fluid secretion and epidermal hydration. Dysfunction and/or abnormal expression of AQPs have been associated with several chronic diseases including epilepsy, cerebral edema, glaucoma, obesity, and cancer. In cancer, several isoforms were found overexpressed and three of them (AQP3, AQP8 and AQP9) can also transport H2O2. This small molecule can be toxic, but at lower concentration can act as second messenger in signaling pathways responsible for cancer cell migration and proliferation. Considering the importance of the AQPs in the initiation, promotion and progression of cancer, we first evaluated the effect of lipid peroxidation on the activity of a yeast aquaporin (AQY1), using a Saccharomyces cerevisiae oxidative stress model. In addition, we investigated the ability of mammalian AQPs to transport H2O2 using a S. cerevisiae heterologous expression model. In this case, the yeast strain used was previously deleted of endogenous aquaporins and transformed with mammalian AQPs, allowing to distinguish the function of each individually cloned isoform. It was identified AQPs with promising results and their function was validated in mammalian cell lines. On the other hand, the expression level of AQP1, AQP3 and AQP5 was evaluated in cancer cells after treatment with H2O2 to assess their gene regulation under conditions of oxidative stress. Finally, the expression level of AQP1, AQP3 and AQP5 was evaluated in several pancreatic biopsies in order to determine potential biomarkers for diagnostic and prognostic. The results obtained and described during this work showed that increased levels of membrane PUFAs triggered AQY1 expression, and its activity is impaired by HNE. Also, our data revealed the ability of AQP5, that is found overexpressed in tumors, as a H2O2 channel that can affect redox signaling. In addition, novel regulatory mechanism at mRNA level was detected in breast and colon cancer cells that may be involved in carcinogenesis. Finally, we show that AQP1, AQP3 and AQP5 can be used as biomarkers for pancreatic ductal adenocarcinoma prognostic and diagnostic. These results open a new perspective to assess the underlying molecular mechanisms of AQPs in signaling pathways associated with cancer and the possible interplay with cell oxidative stress response.