The Synergistic Effect of TRPV1 on Oxidative Stress-Induced Autophagy and Apoptosis in Microglia

Abstract

Stroke mostly including ischemic stroke is the second leading mortality and disability worldwide. Oxidative stress injury occurred during ischemic stroke treatment generally. A high amount of reactive oxygen species (ROS) is involved in oxidative stress induction. Transient receptor potential vanilloid 1 (TRPV1) has been shown to regulate oxidative stress and apoptosis in microglia; however, the detailed mechanisms remain unclear. We aimed to explore whether autophagy-regulated oxidative stress and apoptosis are associated with TRPV1. The model of oxygen and glucose deprivation (OGD/R) in microglia was established. The siRNA of Atg5 and inhibitors and agonists of both autophagy and TRPV1 were involved in our study. Autophagy-related markers Atg5, LC3II/LC3I, and Beclin-1 were measured, and the autophagosome was observed under a transmission electron microscope (TEM). Caspase 3 was detected using ELISA. ROS and JC-1 were detected using flow cytometry. Apoptosis was observed by TUNEL. The results indicated that oxidative stress-induced injury and apoptosis may be impeded by the increasing autophagy, and TRPV1 inhibition could suppress the OGD/R-induced autophagy of microglia. However, the effect of TRPV1’s inhibitor on oxidative stress and apoptosis was not obvious when the autophagy was blocked. These findings suggested that TRPV1 may exhibit antioxidative and antiapoptosis effect on OGD/R-induced microglia. However, the experimental results do not fully demonstrate that the TRPV1-mediated antioxidative and antiapoptosis effect is through the affecting autophagy entirely.

Effect of Different Doses of Capsaicin Administration and Titanium Implant Osseointegration

“…TRPV1 is directly related to oxidative stress in many studies including hippocampus, pain, ischemia-reperfusion, and brain damage [45,46]. We can explain the suppression of oxidative damage in capsaicin groups with TRPV1, which emerged in the study of TRPV1 of capsaicin.…”

Transient receptor potential ion channels and cerebral stroke

“…In addition, an in vitro OGD/reoxygenation (OGD/R) model has been established to induce cerebral I/R injury. In the in vitro OGD/R microglial model, TRPV1 could partly activate OGD/R‐induced microglial autophagy, which impedes oxidative stress‐induced injury and apoptosis (Huang et al., 2021 ; Lin et al., 2022 ). Based on the previous result, 6‐gingerol treatment, which possesses anti‐apoptotic and anti‐inflammatory effects, was employed and was shown to significantly attenuate cerebral infarct volume, improve brain edema and neurological scores, and reverse brain histomorphological damage after I/R injury (Luo et al., 2021 ).…”

Microglial autophagy in cerebrovascular diseases

“…Huang et al found that primary microglia produced large amounts of reactive oxygen species (ROS) due to oxidative stress in OGD/R injury. Additionally, they revealed that enhanced autophagy could reduce the level of ROS and reduce oxidative stress-related apoptosis ( Huang T. et al, 2021 ), whereas Chen et al (2016) found that inhibition of autophagy could reduce microglial apoptosis/death in OGD/R injury in BV2 microglia. Yang et al (2014c) also demonstrated that autophagy promoted hypoxia-induced cell death in primary microglia.…”