Regulation and role of Acyl-CoA synthetase 4 in glial cells  

MELINA DATTILO; YANINA BENZO; HERRERA, LUCIA; JESICA PRADA; LOPEZ PAULA; CARUSO CARLA; LASAGA MERCEDES; GARCIA, CORINA ILEANA; CRISTINA PAZ; PAULA MARIANA MALOBERTI

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2020

0960-0760

Acyl-CoA synthetase 4 (Acsl4), an enzyme involved in arachidonic acid (AA) metabolism,participates in physiological and pathological processes such as steroidogenesis andcancer. The role of Acsl4 in neurons and in nervous system development has also beendocumented but little is known regarding its functionality in glial cells. In turn, severalprocesses in glial cells, including neurosteroidogenesis, stellation and AA uptake, areregulated by cyclic adenosine monophosphate (cAMP) signal. In this context, the aim ofthis work was to analyze the expression and functional role of Acsl4 in primary ratastrocyte cultures and in the C6 glioma cell line by chemical inhibition and stablesilencing, respectively. Results show that Acsl4 expression was regulated by cAMP inboth models and that cAMP stimulation of steroidogenic acute regulatory protein mRNAlevels was reduced by Acsl4 inhibition or silencing. Also, Acsl4 inhibition reducedprogesterone synthesis stimulated by cAMP and also affected cAMP-induced astrocytestellation, decreasing process elongation and increasing branching complexity. Similareffects were observed for Acsl4 silencing on cAMP-induced C6 cell morphological shift.Moreover, Acsl4 inhibition and silencing reduced proliferation and migration of both celltypes. Acsl4 silencing in C6 cells reduced the capacity for colony proliferation andneurosphere formation, the latter ability also being abolished by Acsl4 inhibition. In sum,this work presents novel evidence of Acsl4 involvement in neurosteroidogenesis and themorphological changes of glial cells promoted by cAMP. Furthermore, Acsl4 participatesin migration and proliferation, also affecting cell self-renewal. Altogether, these findingsprovide insights into Acsl4 functions in glial cells.