Calreticulin Binds to Fas Ligand and Inhibits Neuronal Cell Apoptosis Induced by Ischemia-Reperfusion Injury

Abstract

Background. Calreticulin (CRT) can bind to Fas ligand (FasL) and inhibit Fas/FasL-mediated apoptosis of Jurkat T cells. However, its effect on neuronal cell apoptosis has not been investigated. Purpose. We aimed to evaluate the neuroprotective effect of CRT following ischemia-reperfusion injury (IRI). Methods. Mice underwent middle cerebral artery occlusion (MCAO) and SH-SY5Y cells subjected to oxygen glucose deprivation (OGD) were used as models for IRI. The CRT protein level was detected by Western blotting, and mRNA expression of CRT, caspase-3, and caspase-8 was measured by real-time PCR. Immunofluorescence was used to assess the localization of CRT and FasL. The interaction of CRT with FasL was verified by coimmunoprecipitation. SH-SY5Y cell viability was determined by MTT assay, and cell apoptosis was assessed by flow cytometry. The measurement of caspase-8 and caspase-3 activity was carried out using caspase activity assay kits. Results. After IRI, CRT was upregulated on the neuron surface and bound to FasL, leading to increased viability of OGD-exposed SH-SY5Y cells and decreased activity of caspase-8 and caspase-3. Conclusions. This study for the first time revealed that increased CRT inhibited Fas/FasL-mediated neuronal cell apoptosis during the early stage of ischemic stroke, suggesting it to be a potential protector activated soon after IRI.

Kaempferol Protects Against Cerebral Ischemia Reperfusion Injury Through Intervening Oxidative and Inflammatory Stress Induced Apoptosis

“…The inflammatory response makes neurological injury in a worse situation and promotes neural cells apoptosis (Anusha et al, 2017). A large number of evidences showed that the pro-inflammatory cytokines released in the periphery and neuronal apoptosis induced by cerebral I/R may occur potential injury to the hippocampal cells, which are associated with memory and learning functions (Chen et al, 2015). TNF-a, IL-1b, and IL-6 are reported as major mediators in several central nervous systems, and increased level of them related to pathological mechanisms of secondary damage, including neuronal cells apoptosis or death (Fan et al, 2014).…”

DAMP—Induced Allograft and Tumor Rejection: The Circle Is Closing

“…); the fade‐in of the clue to a possible role of ischemia reperfusion injury in such a scenario (leading to an alloimmune response) is purely speculative, though based on data from other lines of studies on models of postischemic reperfusion injury (Refs. ). Ag, (tumor‐associated) antigen; ATP, adenosine triphosphate; CALR, calreticulin; CXCL10, chemokine (C–X–C motif) ligand 10; CXCR3, CXC chemokine receptor 3; DAMP, damage‐associated molecular pattern; dsRNA, double‐stranded RNA; ER, endoplasmic reticulum; HMGB1, high mobility group box 1; ICD, immunogenic cell death; IDC, immature dendritic cell; mDC, mature dendritic cell; UPR, unfolded protein response; NLRP3, NOD‐like receptor family, pyrin domain containing 3; P2X7R, purinergic P2X 7 receptor; RIG‐I, retinoic acid‐inducible gene‐I; TLR, Toll‐like receptor.…”

“…The crucial question in regard to such future studies is: Is there an “allo‐ICD” in analogy to an ICD of cancer cells; in other words, is there a specific DAMP signature in allografts required to cause allograft rejection? At least the four therapy‐induced mandatory factors to promote tumor ICD (CALR, eATP, HMGB1, and type I IFN/CXCL10) have been shown to be implicated in IRI as well (compare Figure ).…”

Origin and Consequences of Necroinflammation

“…This may help to explore an "allo-ICD" as compared with an ICD in cancer. At least the four therapy-induced mandatory factors promoting tumor ICD (CALR, eATP, HMGB1, and type I IFN/CXCL10) have been shown to be implicated in IRI as well (84,174,255,617,636,639,698) (compare FIGURE 11).…”