Distinctive regulation of SREBP1 and SREBP2 by hypertonicity.

CASALI, CECILIA IRENE; WEBER, KAREN; FERNANDEZ TOME, MARIA DEL CARMEN

Mar del Plata, Buenos Aires, Argentina

Congreso; LI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015

Distinctive regulation of SREBP1 and SREBP2 by hypertonicity Casali, C*, Weber, K*and Fernández, MC.Biología Celular y Molecular, Fac. Farmacia y Bioquímica, UBA. IQUIFIB-CONICET. CABA. Argentina. We previously showed that environmental osmolarity regulates phospholipid synthesis and fatty acid storage in (TG) molecules. It is known that both phospholipid and fatty acid synthesis can be regulated by the transcriptional activation of their biosynthetic enzymes which may be mediated by the transcription factor sterol response element binding protein (SREBP). Two isoforms have been reported: SREBP1 and SREBP2. In the present work, we wanted to evaluate whether changes in environment osmolarity can modulate SREBP1 and/or SREBP2 activities by measuring their mRNA levels, protein expression and localization in renal cells. To do this, MDCK cells were grown in isotonic (298 mOsm/Kg H2O) and NaCl-hypertonic (520 mOsm/Kg H2O) media. The results showed that both SREBP1 and 2 are expressed in MDCK cells in basal conditions. Hypertonic medium increased SREBP1 and SREBP2 mRNA levels showing the highest levels at 24 h. SREBP2 protein also showed an increase at 24 h of treatment. By fluorescence microscopy, we found that SREBP1 and SREBP2 are located in different subcelular compartments. Such a distribution was dependent on MAPK pathways since pretreatment with U0126 changed the location pattern of SRBP1 and U0126, SB202190 and SP600125 changed SREBP2 localization. This different behavior may be responsible for lipid regulation in hypertonicity. *Both are considered first authors