CONICET | Buscador de Institutos y Recursos Humanos

Cellular responses induced by stress are essential for the survival of cells under adverse conditions. These responses, resulting in cell adaptation to the stress, are accomplished by a variety of processes at the molecular level. Some responses are common to different stresses, whereas others are specific. After an alteration in homeostatic conditions, intracellular signalling processes link the sensing mechanism to adaptive or compensatory changes in gene expression. Stress usually results in cell cycle delay until damage is repaired, enhancing cell survival or inducing apoptosis. The accumulation of unfolded proteins in the endoplasmic reticulum (ER) represents a cellular stress induced by multiple stimuli and pathological conditions (hypoxia, oxidative injury, high-fat diet, hypoglycaemia, protein inclusion bodies and viral infection). ER stress triggers a series of signal transduction with the aim to ameliorate the accumulation of unfolded proteins in the ER. When these events are severe they can induce cell death probably in a serin-protease dependent way in fibroblasts. Renal medullary cells are normally exposed to variable and high concentrations of NaCl as part of the urinary concentrating system. Despite such adverse conditions, renal cells still survive and function by activating the transcription of various osmoprotective genes. The ability of cells to adapt to hyperosmotic stress involves early responses in which ions move across cell membranes and late responses characterized by increased synthesis of membrane transporters essential for uptake of organic osmolytes or of enzymes involved in their synthesis. There is also an enhanced synthesis of molecular chaperones and transcription factors like TonEBP/NFAT5 which induce the expression of osmoprotectives genes such us cyclooxygenase 2 (COX-2). The goal of these responses is to maintain cellular homeostasis and survive.