PAL31 may play an important role as inflammatory modulator in the repair process of the spinal cord injury rat

Abstract

Abbreviations used: aFGF, acidic fibroblast growth factor; Anp, acidic nuclear protein; ED1, ectodermal dysplasia 1; GFP, Green Fluorescent Protein; IEF, isoelectric focusing; IFN-c, interferon-c; IL-1, interleukin-1; iNOS, inducible nitric oxide synthase; IpG, immobilized pH gradient; LPS, lipopolysaccharide; MCP-1, macrophage chemoattractant protein 1; NO, nitric oxide; NOS, nitric oxide synthase; PAL31, proliferation related acidic leucine-rich protein; PKA, protein kinase A; SCI, spinal cord injury; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; siRNA, small interfering RNA; STAT-1, signal transducer and activator of transcription-1; TNF-a, tumor necrosis factor-a. AbstractFunctional regeneration in a complete T8 transection model Cheng et al. (1996) and most recently, acidic fibroblast growth factor (aFGF; also known as FGF-1) involved in the repair process of the spinal cord injury (SCI) rat Tsai et al. (2008) have been reported. To further reveal the mechanism of the repair process of SCI, in additionally, we have identified a 30 kDa specific protein kinase A substrate induced at 6 days after SCI. However, the induction of the transducing signal was reduced in samples treated with aFGF. The 30 kDa protein was purified and identified by mass spectrometry as a novel protein, PAL31. The results of immunohistochemical study showed that PAL31 is abundantly expressed in the epicenter of the injured spinal cord and colocalizes with ED1-positive cells (macrophages) and CD8 T lymphocytes. Over-expression of PAL31 in RAW 264.7 cells resulted in the down-regulation of macrophage chemoattractant protein 1, inducible nitric oxide synthase, and signal transducer and activator of transcription-1. However, knockdown of PAL31 by small interfering RNA seems to lead to apoptosis when the cells were treated with inflammatory inducers. These experimental results suggest that PAL31 may involve in the modulation of the inflammatory response and, at the same time, prevent apoptosis process of macrophage after SCI. Keywords: apoptosis, inducible nitric oxide synthase, inflammation, macrophage chemoattractant protein 1, PAL31, signal transducer and activator of transcription-1, spinal cord injury.

Chinese Angelica Polysaccharide (CAP) Alleviates LPS-Induced Inflammation and Apoptosis by Down-Regulating COX-1 in PC12 Cells

“…Inflammatory response contributes a lot in the regulation of SCI pathogenesis, and seems to play a pivotal role in nerve injury and regenerative response [8]. In addition, inflammatory response may contribute to the apoptosis of neurons and oligodendrocytes as well as to the loss of neuronal function [9]. Therefore, anti-inflammation is thought to be critical for decrease of secondary degeneration and the functional deficit following SCI.…”

Cytoprotective and anti-inflammatory effects of PAL31 overexpression in glial cells

“…In our previous study, PAL31 was found to express in the infiltrated macrophages in the epicenter of the injured spinal cord [15]. The amount of PAL31 reached its peak level over 6 days after transection of spinal cord.…”

“…Previously, we had identified a phospho-motif in PKA substrates that correlated with SCI rat neural regeneration [15]. This novel molecule was identified as a proliferation related acidic leucine-rich protein (PAL31) with molecular weight of 31 kDa.…”

“…PAL31 had been discovered in the developing nervous system and its expression level decreased following maturation. The functions of PAL31 has been discovered that participated in cell cycle progression [16], caspase-3 inhibition [17], and inflammatory modulation [15]. Interestingly, PAL31 was found to express in the infiltrated macrophages in the epicenter of the injured spinal cord and the amount of PAL31 reached its peak level over 6 days after transection of spinal cord [15].…”

Receptor for Advanced Glycation End Products (RAGE) and Its Ligands: Focus on Spinal Cord Injury

“…After SCI, inflammation is a major response and source of secondary injury, considering that it modulates the pathogenesis of acute and chronic SCI [36]. Inflammatory responses cause apoptosis of neurons and glia, as well as glial scar formation and the decline of neuronal function [37]. Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), are expressed by CNS cells, including microglia, astrocytes, neurons, and oligodendrocytes at early time points (one to three hours) after SCI [38,39,40].…”