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Estrogen Attenuates Hypoxia-Induced TRPV1 Activation and Calcium Overload via HIF-1α Suppression in MCF-7 and CHO Cells     
Yazarlar (1)
Doç. Dr. Bilal ÇİĞ Doç. Dr. Bilal ÇİĞ
Kırşehir Ahi Evran Üniversitesi, Türkiye
Devamını Göster
Özet
Hypoxia is a major global health concern, particularly in premature infants and cancer, where it promotes intracellular calcium accumulation and cell death. The transient receptor potential vanilloid 1 (TRPV1) channel has been implicated in calcium dysregulation and oxidative stress under hypoxic conditions, while estrogen (17β-estradiol, E2) is known to modulate TRPV1 activity and redox balance. This study aimed to investigate the impact of E2 on TRPV1 expression, hypoxia-inducible factor-1α (HIF-1α), and calcium signaling in MCF-7 breast cancer cells (ERα-positive) and TRPV1-transfected CHO cells (ERα-negative). Four experimental groups were established: normoxia, E2, hypoxia, and hypoxia + E2. Hypoxia was induced by CoCl2 (200 µM, 24 h), while E2 treatment was applied at 10 nM for 24 h. Western blot analysis revealed that both TRPV1 and HIF-1α expression were upregulated under hypoxia but significantly reduced by E2. Fura-2 fluorescence assays revealed that hypoxia increased cytosolic Ca2+ levels, whereas E2 reversed this elevation. Moreover, TRPV1 activation by capsaicin induced marked Ca2+ influx under hypoxia, which was attenuated by E2 treatment. These findings demonstrate that E2 mitigates hypoxia-induced toxicity by modulating TRPV1-mediated Ca2+ signaling and HIF-1α expression, underscoring the protective role of E2 and identifying TRPV1 as a potential therapeutic target in estrogen-responsive tumors.
Anahtar Kelimeler
17β-estradiol | calcium signaling | CHO | HIF-1α | hypoxia | MCF-7 | TRPV1
Makale Türü Açık Erişim Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale
Dergi Adı International Journal of Molecular Sciences
Dergi ISSN 1661-6596 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCOPUS, SCI-Expanded
Dergi Grubu Q1
Makale Dili İngilizce
Basım Tarihi 11-2025
Cilt No 26
Sayı 22
Sayfalar 1 / 15
DOI Numarası 10.3390/ijms262211110
Makale Linki https://www.mdpi.com/1422-0067/26/22/11110