.png){kind=icon}
.png){kind=icon}
Return
Acid-sensing ion channel 1a contributes to the calcium/calmodulin-dependent ferroptosis and aggravates intervertebral disc degeneration
.png){kind=icon}
OA
AI
L
J
L
Y
X
C
C
张
R
C
DOI：10.1080/13510002.2026.2618396.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
ObjectivesAcid-sensing ion channel 1a (ASIC1a) functions as an extracellular acid sensor, with its activation frequently associated with age-related diseases. We aim to investigate the expression pattern of ASIC1a in the ferroptosis of degenerated nucleus pulposus (NP) tissues and NP cells (NPCs), and explore whether ASIC1a-mediated calcium influx regulates ferroptosis in NPCs through the calcium/calmodulin pathway during intervertebral disc degeneration (IVDD).MethodsWe use NP tissues, NPCs, and Transcriptome sequencing to investigate the effects and mechanism of ASIC1a in ferroptosis during the progression of IVDD.ResultsElevated expression of ASIC1a was associated with the progression of ferroptosis in human degenerated NP tissues. Meanwhile, the expression of ASIC1a remarkably increased as acid-induced ferroptosis progressed in human NPCs. Besides, transcriptomic analysis identified that inhibition of ASIC1a attenuates ECM degradation and ferroptosis. We then confirmed the overexpression of ASIC1a promoted the progression of ferroptosis and ECM degradation in human NPCs in vitro. Moreover, the ferroptosis of NPCs induced by ASIC1a overexpression was ameliorated by the treatment of BAPTA-AM (the intracellular calcium chelator) or calmidazolium (the calmodulin antagonist). ASIC1a mediated acid-induced ferroptosis via calcium/calmodulin signaling in human NPCs. The in vivo study further indicated that the inhibition of ASIC1a activation ameliorated the IVDD by suppressing ferroptosis in the rat model.ConclusionThis study demonstrated that ASIC1a increased as ferroptosis progressed in human NP tissues and human NPCs. The acid-induced ASIC1a upregulation caused increased calcium levels and contributed to the ferroptosis in NPCs partially mediated by calcium/calmodulin signaling.
Keywords:
ASIC1a
ferroptosis
calcium
nucleus pulposus
intervertebral disc degeneration
Journal
IF:
7.4
Papers:
1.3K
Citations:
2.4K
Organization
Cited Papers