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Expression of plasma membrane (PMCA) and sarco/endoplasmic reticulum (SERCA) Ca 2+ ‐ATPase pumps in cellular model of Huntington disease (1138.8)
Author(s) -
Cesca Federica,
Dubsky de Wittenau Giorgia,
Curcio Francesco,
Lonigro Renata
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1138.8
Subject(s) - serca , huntingtin , plasma membrane ca2+ atpase , endoplasmic reticulum , microbiology and biotechnology , calcium pump , homeostasis , biology , calcium metabolism , huntingtin protein , calcium , chemistry , atpase , mutant , biochemistry , gene , organic chemistry , enzyme
Deregulation of calcium homeostasis is involved in the etiology of Huntington’s disease (HD). We investigated the expression level of calcium pumps in cellular models of HD derived from murine embryonic striatum. We compared the steady‐state level of PMCA1‐4 and SERCA2,3 pumps in wild‐type and mutant cell lines, both in undifferentiated and in glial differentiated conditions. Comparison between mutant and wild‐type cell lines in the undifferentiated condition show that: i. the level of PMCA1‐4 RNA and protein is comparable except for a reduction of PMCA3 RNA. ii. SERCA2 protein level is significantly reduced while SERCA3 protein level is significantly increased, suggesting a role for these pumps in calcium homeostasis deregulation in HD. There is no correspondence between SERCA proteins and their respective RNA, probably due to post‐transcriptional regulatory mechanism/s. In a rat striatal‐derived cellular model of HD in which huntingtin expression is inducible by doxycicline, we confirmed the reduction of SERCA2 protein level as a huntingtin expression‐dependent event. These data suggest that the reduction of SERCA2 pump could be an early event occurring in HD. Comparison between mutant and wild‐type cell lines in the glial differentiated condition show that PMCA1 and PMCA2 protein levels are reduced, while their respective RNA are increased suggesting a post‐transcriptional regulatory mechanism/s for calcium homeostasis deregulation also in glial differentiated cells. Grant Funding Source : SNO ‐ Gobessi Fund