Expression and localization of estrogen receptor α in the C2C12 murine skeletal muscle cell line
Open accessAbstract
The classical model of 17beta-estradiol action has been traditionally described to be mediated by the estrogen receptor (ER) localized exclusively in the nucleus. However, there is increasing functional evidence for extra nuclear localization of ER. We present biochemical, immunological and molecular data supporting mitochondrial-microsomal localization of ER alpha in the C2C12 skeletal muscle cell line. We first established [(3)H]17beta estradiol binding characteristics in whole cells in culture. Specific and saturable [(3)H]17beta estradiol binding sites of high affinity were then detected in mitochondrial fractions (K(d) = 0.43 nM; B(max) = 572 fmol/mg protein). Immunocytological studies revealed that estrogen receptors mainly localize at the mitochondrial and perinuclear level. These results were also confirmed using fluorescent 17beta estradiol-BSA conjugates. The immunoreactivity did not translocate into the nucleus by 17beta-estradiol treatment. Western and Ligand blot approaches corroborated the non-classical localization. Expression and subcellular distribution of ER alpha proteins were confirmed in C2C12 cells transfected with ER alpha siRNA and by RT-PCR employing specific primers. The non-classical distribution of native pools of ER alpha in skeletal muscle cells suggests an alternative mode of ER localization/function.
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Subpopulations of ERα and ERβ exist in mitochondria, although it is still unclear if they can directly regulate mtDNA transcription.
“Interestingly, it was found that subpopulations of ERα and ERβ exist in mitochondria, although it is still unclear if they can directly regulate mtDNA transcription (132–134).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [133]
Both ERα and ERβ are expressed in skeletal muscles of mice and humans.
“Both ERα and ERβ are expressed in skeletal muscles of mice and humans [10,12,13,14].”
From Phytoecdysteroids and Anabolic Effect of Atriplex dimorphostegia: UPLC-PDA-MS/MS Profiling, In Silico and In Vivo Models (2023) · cites this paper as [14]
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- Authors
- Milanesi, L., de Boland, A. R., & Boland, R.
- Affiliations
- Universidad Nacional del Sur (AR)
- Corresponding author
- Boland, Ricardo
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2008-03-17
- Volume
- 104
- Issue
- 4
- Pages
- 1254-1273
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W2007979384
- Cited by
- 64
- References
- 52
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 5 · 2012: 3
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Agencia Nacional de Promoción Científica y Tecnológica (CONICET)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- estrogen receptor alpha, mitochondrial localization, skeletal muscle cells, C2C12 myoblasts, subcellular localization, nuclear translocation, siRNA knockdown
- MeSH terms
- Animals, Cell Line, Estradiol, Female, Immunohistochemistry, Microsomes, Mitochondria, Muscle, Skeletal, Protein Transport, Estrogen Receptor alpha, Mice
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