Involvement of Src-Suppressed C Kinase Substrate in Neuronal Death Caused by the Lipopolysaccharide-Induced Reactive Astrogliosis

Abstract

Src-suppressed C kinase substrate (SSeCKS), a protein kinase C substrate, is a major lipopolysaccharide (LPS) response protein, regulating the inflammatory process. In the process of spinal inflammatory diseases by LPS intraspinal injection, expression of SSeCKS in the spinal cord was increased, mainly in active astrocytes and neurons. Induced SSeCKS was colabeled with terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling (an apoptosis maker) in the late inflammation processes. These results indicated that SSeCKS might correlate with the inflammatory reaction and late neurodegeneration after LPS injection. A cell type-specific action for SSeCKS was further studied within C6 cells and PC12 cells. Knockdown of SSeCKS by small-interfering RNAs (siRNAs) blocked the LPS-induced inducible nitric oxide synthase (iNOS) expression in C6 cells, while overexpression SSeCKS enhanced iNOS expression. SSeCKS is also participated in regulation of PC12 cell viability. Loss of SSeCKS rescued PC12 cell viability, and excessive SSeCKS exacerbated the cell death upon conditioned medium and tumor necrosis factor-alpha exposure. This study delineates that SSeCKS may be important for host defenses in spinal inflammation and suggests a valuable molecular mechanism by which astrocytes modify neuronal viability during pathological states.

The Relationship Between Src-Suppressed C Kinase Substrate and β-1,4 Galactosyltransferase-I in the Process of Lipopolysaccharide-Induced TNF-α Secretion in Rat Primary Astrocytes

“…In current study, we also showed that LPS induced astrocytes activation and up-regulated the expression of SSeCKS in astrocytes. These results are in agreement with our previous study (Shen et al 2009;Wang et al 2010). We consider that SSeCKS binds PKC in a phosphatidylserine-dependent manner and is also a major PKC substrate in vitro and in vivo.…”

Microglial VPS35 deficiency regulates microglial polarization and decreases ischemic stroke-induced damage in the cortex

“…Neuronal death/injury often leads to an increase of reactive astrocytes, a key event for brain inflammation [27]. We then examined glial fibrillary acidic protein (GFAP) marked reactive astrocytes in control and VPS35 CX3CR1 cortical brain in response to ischemia/stroke.…”

Methanol extract of Osbeckia stellata suppresses lipopolysaccharide- and HCl/ethanol-induced inflammatory responses by inhibiting Src/Syk and IRAK1

“…4F), suggesting that these enzymes are important signaling components in LPS-triggered inflammatory responses of macrophages. Indeed, the activation of these enzymes in many different inflammatory events triggered by LPS, poly(I:C), and peptidoglycan has been reported (Check et al, 2010;Wang et al, 2010).…”