Piezo1 mediates neuron oxygen-glucose deprivation/reoxygenation injury via Ca2+/calpain signaling
Introduction
Brian ischemia/reperfusion injury (IRI) is common and even inevitable during some types of surgery such as cardiac surgery and carotid endarterectomy [1,2]. Apoptosis constitutes a major part of neuron death following IRI and various interventions have been tried [3]. However, the treatment efficacy remain unsatisfactory and more new and powerful molecular targets or strategies are still needed [4].
Calcium ion (Ca2+) is a critical regulator of neuron fate during IRI [5]. Calcium overload during reperfusion can induce endoplasmic reticulum stress and neuron apoptosis by activate calpain signaling [6,7] and inhibition of Ca2+/calpain signaling has been thought to be a promising way to counteract brain IRI [8,9].
In 2010, researchers discovered Piezo1 as a mechanical stimulation-, such as membrane stretch, static pressure and shear stress, activated ion channel [10]. Recently, it is found that Piezo channel can also be modulated by voltage and switch to a purely voltage-gated mode [11]. Both modes of activation increased nonselective cation permeability and mainly calcium influx [[11], [12], [13]]. Moreover, a role of Ca2+/calpain signaling in Piezo1-mediated vascular development has been postulated [13,14]. A study also reveals that Piezo1 regulates mechanically activated currents in the Neuro2A cell line [10]. However, whether Piezo1 is expressed in neurons and plays a role in IRI-induced neuron apoptosis is not known. In this study, we first observed that the expression level of Piezo1 was up-regulated after hypoxia/reoxygenation in PC12 cells and rat brain cortex and further explored the role of Piezo-1/Ca2+/calpain signaling in hypoxia/reoxygenation injury.
Section snippets
Cell culture
The neuron-like PC12 cells (highly differentiated) were purchased from Kunming Institute of Zoology (Kunming, China) and cultured in high glucose Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (Gibco, USA), 100 U/mL penicillin and 100 μg/mL streptomycin (Gibco, USA). The cells were incubated in an incubator at 37 °C with saturated humidity and 5% CO2 plus 95% O2. The culture medium was changed every other day and experiments were carried out when the cells adhered
Piezo1 was expressed in adult rat brain cortex and PC12 cells
Immunohistochemical staining showed that Piezo1 was expressed in the cerebral cortex of adult rats (Fig. 1Aa). Immunofluorescence results also confirmed that Piezo1 protein was expressed in adult rat brain cortex and PC12 cells and localized in both the endoplasmic reticulum and the nucleus (Fig. 1Ab and c).
Piezo1 expression was increased in PC12 cells and rat MCAO brain cortex
The expression of Piezo1 was increased in PC12 cells after 24-h reoxygenation as compared with control and cells with other durations of reoxygenation (Fig. 1Ba and b). The following
Discussion
Piezo1 ion channel is a new type of non-selective mechanically sensitive ion channel discovered in recent years. In this study, we explored the role of the Piezo1 in neuron OGD/R injury and found that Piezo1 could regulate the apoptosis of neurons after OGD/R injury through the Ca2+/calpain signaling.
Studies have shown that inhibition of Piezo1 expression in human osteosarcoma (OS) cells could reverse stretch-induced apoptosis and apoptosis-related gene expression [20]. More recently, Yang Q
Disclosure
The authors declare no conflict of interests.
Acknowledgement
This study was supported by National Natural Science Foundation of China (No. 81502182 and No. 81400893), National Natural Science Foundation of Beijing, China (No. 7142169) and CPLA Youth Training Project for Medical Science (17QNP030).
References (28)
- et al.
Ischemic stroke: advances in diagnosis and management
Emerg. Med. Clin. N. Am.
(2017) - et al.
Calcium, ischemia and excitotoxicity
Cell Calcium
(2010) - et al.
Neuroprotective effects of propofol on ER stress-mediated apoptosis in neuroblastoma SH-SY5Y cells
Eur. J. Pharmacol.
(2014) - et al.
Piezo1 channels in vascular development and the sensing of shear stress
Curr. Top. Membr.
(2017) - et al.
Neuroprotective effects of berberine on stroke models in vitro and in vivo
Neurosci. Lett.
(2008) - et al.
Direct activation of cytosolic Ca2+ signaling and enzyme secretion by cholecystokinin in human pancreatic acinar cells
Gastroenterology
(2008) Perioperative stroke
N. Engl. J. Med.
(2007)- et al.
Perioperative stroke
Can. J. Anaesth.
(2016) - et al.
Apoptosis and acute brain ischemia in ischemic stroke
Curr. Vasc. Pharmacol.
(2017) - et al.
Calpains are downstream effectors of bax-dependent excitotoxic apoptosis
J. Neurosci.
(2012)
Potential use of calpain inhibitors as brain injury therapy
Calpain-2 as a therapeutic target for acute neuronal injury
Expert Opin. Ther. Targets
Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels
Science
Voltage gating of mechanosensitive PIEZO channels
Nat. Commun.
Cited by (0)
- 1
equal contributors.