Ludmila Zylinska, Tomasz Radzik, Tomasz Boczek, Bozena Ferenc, Maciej Studzian and Lukasz Pulaski
Medical University of Lodz, Poland
Stanford University School of Medicine, USA
University of Lodz, Poland
Institute of Medical Biology of PAS, Poland
Posters & Accepted Abstracts: J Neurol Neurophysiol
Neurodegeneration is a critical process observed in the ageing brain as well as in neuroinflammatory diseases induced by some chemokines. They constitute a large family of structurally-related small molecules that act by G-protein coupled receptors. Chemokine CCL5 can bind CCR1, CCR3 and CCR5 with downstream activation of PLC/IP3R pathway, thereby mobilizes Ca2+ from endoplasmic reticulum (ER). A low basal cytosolic Ca2+ level is maintained predominantly by plasma membrane Ca2+-ATPase (PMCA) existing in 4 isoforms. In our lab the unique function of PMCA has been studied using a suitable model of pseudo-neuronal differentiated PC12 cells. Since PMCA decreases with age, we have also developed the lines with suppressed PMCA2 or PMCA3 isoform to mimic the aging neurons. In both PMCA-reduced lines CCL5 released more Ca2+ from ER and increased a time required for Ca2+ clearance, but reduction of PMCA2 appeared to be more detrimental for the cells than deficiency of PMCA3. Altered PMCAs composition induced some adaptive mechanisms by changes of CCR5 and IP3Rs expression level, which could provide some protection against calcium overload. However, in aging brain increased BBB permeability, augmented leukocytes infiltration, more severe CCL5 action and long-lasting Ca2+ dyshomeostasis may cause that these compensatory mechanisms could not be sufficient for full cells protection.
Ludmila Zylinska PhD, DSc, is a Full Professor and Head of the Department of Molecular Neurochemistry, Medical University of Lodz, Poland. Her scientific interests are related to regulation of neuronal calcium homeostasis with particular attention brought on plasma membrane calcium pumps in the CNS, as well as on molecular mechanisms of calcium-dependent processes that regulate neuronal transmission in physiological and pathological conditions. She has published more than 60 papers in the areas of Biochemistry, Neuroscience and Cell Biology.
E-mail: ludmila.zylinska@umed.lodz.pl
