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Dietary vitamin D3 supplementation at 50× the adequate intake decreases calbindin d28k and endoplasmic reticulum stress and increases apoptosis, suggesting toxicity, in the female transgenic G93A mouse model of amyotrophic lateral sclerosis
Author(s) -
TaheriShalmani Siavash,
Shahsavar Shayan,
Gianforcaro Alexandro,
Solomon Jesse Adam,
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.644.1
Subject(s) - amyotrophic lateral sclerosis , endoplasmic reticulum , endocrinology , medicine , unfolded protein response , vitamin d and neurology , apoptosis , toxicity , chop , biology , microbiology and biotechnology , biochemistry , disease , chemotherapy
Background We previously showed that dietary vitamin D 3 (D 3 ) at 50× the adequate intake increased functional capacity in the transgenic G93A mouse model of amyotrophic lateral sclerosis (ALS), with females exhibiting signs of D 3 toxicity. ALS is a progressive neuromuscular disease resulting in the death of upper and lower motor neurons. Objective In this pilot study, we analyzed the quadriceps of G93A mice following dietary D 3 supplementation at 50× the AI 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, 41 G93A mice were provided food ad libitum with either adequate (AI; 1 IU D 3 /g feed; 12 M, 11 F) or high (HiD; 50 IU D 3 /g feed; 10 M, 8 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, HiD had 33% lower calbindin d28k (P = 0.066), 68% lower CHOP (P = 0.074), and 242% higher bax/bcl2 ratio (P = 0.080) vs. AI. HiD males showed no significant differences vs. AI. Conclusion Dietary D 3 at 50× the AI decreases ER stress in the quadriceps of female G93A mice, but increases apoptosis, which could be due to D 3 toxicity. We hypothesize a dynamic crosstalk between ER stress and calcium trafficking. (Supported by NSERC and Faculty of Health, York University) Grant Funding Source : NSERC and Faculty of Health, York University