Abstract
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein involved in the extracellular matrix and interactions between cells during neural development of the central nervous system (CNS). Oxidative glutamate toxicity is involved in CNS diseases, including epilepsy, Alzheimer’s disease, and ischemic stroke. However, the molecular mechanism of nerve injury is not fully understood in CNS diseases. Herein, the glutamate-induced nerve damage model was used to explore the molecular mechanisms affecting nerve damage. The levels of SPARC and autophagy were increased in glutamate-induced HT22 hippocampal nerve injury. In summary, the current study confirmed that SPARC regulates autophagy in HT22 hippocampal nerve cells, and its knockdown reduces the glutamate-induced HT22 hippocampal nerve injury by inhibiting autophagy. These findings suggested that SPARC plays a crucial role in nerve injury of CNS diseases.
Highlights
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein (MCP) involved in the extracellular matrix (ECM) and interactions between cells by the regulation of growth factor signaling, cytokine signaling, and cell adhesion, proliferation, and metastasis (Bradshaw, 2012)
SPARC has not been shown to be involved in glutamate-induced brain neuronal cell damage, the current study aimed to investigate whether it participates in glutamate-induced neuronal damage via induced autophagy pathway
The following reagents were used in this study: 3-methyladenine (3-MA) (HY-19312) and chloroquine (CQ) diphosphate salt (C6628, MedChemExpress, United States); glutamate (G8415), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (M5655), and dimethyl sulfoxide (DMSO) (D2650) (Sigma–Aldrich, United States). 3-MA, MTT, and CQ diphosphate salt were solubilized in phosphate-buffered saline (PBS)
Summary
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein (MCP) involved in the extracellular matrix (ECM) and interactions between cells by the regulation of growth factor signaling, cytokine signaling, and cell adhesion, proliferation, and metastasis (Bradshaw, 2012). SPARCL-1 (SC-1), known as Hevin, is one of the SPARC family proteins involved in the migration of neurons and the formation of synapses during neural development of the central nervous system (CNS; Jones and Bouvier, 2014). A recent study showed that SPARC and SPARCL-1 are strongly implicated in the regulation of neural factors and excitatory synaptic receptors in the brain (Jones et al, 2011; Gan and Südhof, 2019; Okura et al, 2019). In the AD brain, highly expressed SPARC collocates to Aβ protein deposits and contributes to cerebral inflammation
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