Heterozygous disruption of ALAS1 in mice causes an accelerated age-dependent reduction in free heme, but not total heme, in skeletal muscle and liver
نویسندگان
چکیده
5-Aminolevulinic acid (ALA) is the rate-limiting intermediate in heme biosynthesis vertebrate species; a reaction catalyzed by mitochondrial ALA synthase 1 (ALAS1) enzyme. Previously we reported that knockdown of ubiquitously expressed ALAS1 gene mice disrupts normal glucose metabolism, attenuates function and results prediabetic like phenotype when animals pass 20-weeks age (Saitoh et al., 2018). Contrary to our expectations, cytosolic content heterozygous (A1+/-) were similar WT animals. Therefore, speculated regulatory “free heme” may be reduced an dependent manner A1+/- mice, but not total heme. Here, examine free from skeletal muscle liver using modified acetone extraction method effects aging on comparing amounts at 8–12 weeks 30–36 age, addition mRNA abundance ALAS1. We found age-dependent reduction while showed only slight decrease liver. Total levels no significant difference between young aged mice. levels, indicating expression are major determinant for levels. The pools tissue almost 2-fold larger than tissue, suggesting pool varies across different types. oxygenase (HO-1) mRNA, which proportionally amount heme, those Taken together, this study demonstrates differs tissues, accelerated ALAS1, could account abnormality observed these
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ژورنال
عنوان ژورنال: Archives of Biochemistry and Biophysics
سال: 2021
ISSN: ['1096-0384', '0003-9861']
DOI: https://doi.org/10.1016/j.abb.2020.108721