Estrogen Attenuates Hypoxia-Induced TRPV1 Activation and Calcium Overload via HIF-1α Suppression in MCF-7 and CHO Cells.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

TRPV Cation Channels*/metabolism ; TRPV Cation Channels*/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit*/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit*/genetics ; Calcium*/metabolism ; Estrogens*/pharmacology ; Estradiol*/pharmacology; Calcium Signaling/drug effects ; Cell Hypoxia/drug effects ; Humans ; Animals ; MCF-7 Cells ; CHO Cells ; Cricetulus

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.

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Keywords: 17β-estradiol; CHO; HIF-1α; MCF-7; TRPV1; calcium signaling; hypoxia

0 (TRPV Cation Channels)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SY7Q814VUP (Calcium)
0 (TRPV1 protein, human)
0 (Estrogens)
4TI98Z838E (Estradiol)
0 (HIF1A protein, human)

Date Created: 20251127 Date Completed: 20251127 Latest Revision: 20251130

20260130

PMC12653836

10.3390/ijms262211110

41303593