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Sexual dichotomy in calcium buffering capacity may be dependent on the severity of endoplasmic reticulum stress in the skeletal muscle of the vitamin D3 deficient transgenic G93A mouse model of amyotrophic lateral sclerosis
Author(s) -
Shahsavar Shayan,
TaheriShalmani Siavash,
Solomon Jesse Adam,
Gianforcaro Alexandro,
Hamadeh Mazen Jamal
Publication year - 2013
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.27.1_supplement.644.2
Subject(s) - endoplasmic reticulum , medicine , endocrinology , amyotrophic lateral sclerosis , unfolded protein response , caspase 12 , calcium , serca , vitamin d and neurology , chop , calcium in biology , apoptosis , calpain , biology , microbiology and biotechnology , disease , programmed cell death , caspase , biochemistry , atpase , enzyme
Background We previously demonstrated that dietary vitamin D 3 (D 3 ) restriction hastened the decline in functional capacity following disease onset in the G93A mouse model of amyotrophic lateral sclerosis (ALS). ALS is a progressive neuromuscular disease characterized by the degeneration and death of motor neurons. Objective In this pilot study, we analyzed the quadriceps of G93A mice following dietary D 3 restriction at 2.5% the adequate intake for vitamin D receptor and markers of intracellular calcium trafficking (calbindin d28k, calretinin), endoplasmic reticulum (ER) stress (SERCA2, CHOP) and apoptosis (bax/bcl2 ratio, caspase 12 cleaved/pro ratio). Methods Beginning at age 25 d, 42 G93A mice were provided food ad libitum with either adequate (AI; 1 IU D 3 /g feed; 12 M, 11 F) or deficient (DEF; 0.025 IU D 3 /g feed; 10 M, 9 F) D 3 . At age 113 d, the quadriceps were analyzed for protein content. Differences were considered significant at P ≤ 0.10. Results In females, DEF had 30% lower calbindin d28k (P = 0.075), 69% higher cleaved/pro caspase 12 ratio (P = 0.100), and 103% higher bax/bcl2 ratio (P = 0.057) vs. AI. DEF males had 67% higher CHOP (P = 0.048) vs. AI. Conclusion Dietary D 3 at 2.5% the AI reduces calcium buffering capacity and increases prolonged ER stress‐induced apoptosis in female, but not in male, G93A mice. We hypothesize a reciprocal interaction between ER stress and calcium buffering. (Supported by NSERC and Faculty of Health, York University) Grant Funding Source : NSERC and Faculty of Health, York University