ABSTRACT
Title
Constitutive gender-associated tissue differences of autophagic process
Authors
Campesi I1,2,3,a., Straface E4,a, Galistu A1,3., Occhioni S1,3, Gambardella L4, W Malorni4 and F. Franconi1,2,3
a) the two author contributed equally
1 Department of Pharmacology, University of Sassari,
2 National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy
3 Centre of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari
4 Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy
a) the two author contributed equally
1 Department of Pharmacology, University of Sassari,
2 National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy
3 Centre of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari
4 Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy
Abstract
Autophagy is a lysosomal degradative pathway involved in the intracellular turnover of proteins and cell organelles and has an important role in regulating cell fate in response to stress. We demonstrated a gender disparity in this regard (Malorni et al., 2008; Straface et al., 2009). Under basal conditions autophagic activity is low but can be activated by physiological and pathological conditions in multiple organs. Conversely, autophagy suppression is often associated with certain diseases, including a subset of cancer, neurodegenerative disorders, infectious diseases and inflammatory bowel disorders (Mizushima et al., 2010). In order to investigate if, in basal conditions, sexual autophagic differences could occur in different organs from male and female rats, specific studies have been undertaken. Paraffin-embedded sections from liver, heart and kidney have been analyzed by immunofluorescence microscopy. In particular, a double labeling of LC3 (a marker of autophagosome) and Lamp-1 (a marker of lysosomes) has been carried out to evaluate the formation of autophagolysosomes (a hybrid organelle generated by the fusion of an autophagosome and a lysosome). Analyses conducted by immunofluorescence microscopy clearly indicated an increased expression and colocalization of LC3 and Lamp-1 only in organs from male rats. These results were corroborated by biochemical western blot analyses.
Although the biological significance of this phenomenon remains to be elucidated, we can not rule out the possibility that this constitutive autophagic activity, mainly detectable in organs from male rats, could become a relevant biomarker and a pharmacological target in the long run.
Malorni et al., FEBS Letters 2008
Straface et al., FEBS Letters 2009
Mizushima et al., Cell 2010
Although the biological significance of this phenomenon remains to be elucidated, we can not rule out the possibility that this constitutive autophagic activity, mainly detectable in organs from male rats, could become a relevant biomarker and a pharmacological target in the long run.
Malorni et al., FEBS Letters 2008
Straface et al., FEBS Letters 2009
Mizushima et al., Cell 2010