Heat Shock Protein A12B Research Articles

Prognostic value of plasma heat shock protein A12B levels in patients with multiple organ dysfunction syndrome

Objective The aim of this study was to explore the role of heat shock protein A 12B (HSPA 12B) as a potential prognosis biomarker for multiple organ dysfunction syndrome (MODS).Methods The study involved 30 patients with MODS,including non-survivors (n=16) and survivors (n=14).Thirty patients with systemic inflammatory response syndrome (SIRS) and 15 healthy controls to evaluate the prognostic value of HSPA12B.The levels of plasma HSPA12B and interleukin (IL)-6 were measured by enzyme linked immunosorbent assay (ELISA).Results The level of plasma HSPA12B was significandy higher in patients with MODS than that in other two groups (P＜0.001).There is no differences in HSPA12B levels between SIRS patients and healthy volunteers (P=0.647).Level of HSPA12B in non-survivors was significantly higher than that in survivors (P＜0.05).Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ)score,MODS score,Sequential organ failure assessment(SOFA) score,and length of mechanical ventilation in non-survivors were significantly higher than surviors.For prognostic value of HSPA12B,it has a area under the cure(AUC)of0.826(95％ CI:0.663-0.989,P＜0.01),significantly higher than IL-6.Conclusions Increased plasma HSPA12B within 24 h after onset of MODS can be considered as a potential prognostic biomarker in patients. Key words: Multiple organ dysfunction syndrome; Heat shock protein A12B; Prognosis

Plasma HSPA12B is a potential predictor for poor outcome in severe sepsis.

IntroductionEndothelium-derived molecules may be predictive to organ injury. Heat shock protein (HSP) A12B is mainly located in endothelial cells, which can be detected in the plasma of septic patients. Whether it is correlated with prognosis of sepsis remains unclear.MethodsExtracellular HSPA12B (eHSPA12B) was determined in plasma of septic mice at 6h, 12h, 24h and 48h after cecal ligation and puncture (CLP). It was also detected in plasma of patients with severe sepsis, sepsis, systemic inflammatory response syndrome and healthy volunteers. The predictive value for prognosis of severe sepsis was assessed by receiver operating curve (ROC) and Cox regression analyses.ResultseHSPA12B was elevated in plasma of CLP mice at 6h and peaked at 24h after surgery. A total of 118 subjects were included in the clinical section, including 66 patients with severe sepsis, 21 patients with sepsis, 16 patients with SIRS and 15 volunteers. Plasma eHSPA12B was significantly higher in patients with severe sepsis than in patients with sepsis, SIRS and volunteers. The level of eHSPA12B was also higher in non-survivals than survivals with severe sepsis. The area under the curve (AUC) of eHSPA12B in predicting death among patients with severe sepsis was 0.782 (0.654–0.909) in ROC analysis, much higher than that of IL-6 and IL-10. Cox regression analysis showed that cardiovascular diseases, IL-6 and eHSPA12B were risk factors for mortality in patients with severe sepsis. Survival curve demonstrated a strikingly significant difference between 28-day survival rates of patients with an eHSPA12B lower or not lower than 1.466ng/ml.ConclusionsPlasma eHSPA12B is elevated in both septic mice and patients. It may be a good predictor for poor outcome in patients with severe sepsis.

The Role of HSPA12B in Regulating Neuronal Apoptosis

Heat shock protein A12B (HSPA12B) is the newest member of a recently defined subfamily of proteins distantly related to the 70-kDa family of heat shock proteins (HSP70) family. HSP70s play a crucial role in protecting cells, tissues, organs and animals from various noxious conditions. Here we studied the dynamic expression changes and localization of HSPA12B after middle cerebral artery occlusion (MCAO) with reperfusion induced ischemic insult processes in adult rats. Apoptosis, as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, was also increased in the peri-ischemic cortex compared to non-ischemic hemisphere. The expression of HSPA12B was strongly induced in the ischemic hemisphere of MCAO reperfusion rats in vivo. In vitro studies indicated that the up-regulation of HSPA12B may be involved in oxygen-glucose deprivation-induced PC12 cell death. And knockdown of HSPA12B in cultured differentiated PC12 cells by siRNA showed that HSPA12B inhibited the expression of active caspase-3. Collectively, these results suggested that HSPA12B may be required for protecting neurons from ischemic insults.

Attenuation of cardiac dysfunction by HSPA12B in endotoxin-induced sepsis in mice through a PI3K-dependent mechanism

cardiac dysfunction is a critical manifestation of severe sepsis/septic shock and is responsible for high mortality due to sepsis. Recent evidence suggests that angiogenic factors have a protective effect on sepsis-induced organ damage. Heat shock protein A12B (HSPA12B) is a newly discovered gene that is essential for angiogenesis. We hypothesized that overexpression of HSPA12B would induce protection against endotoxin-induced cardiac dysfunction. to evaluate this hypothesis, we generated transgenic mice overexpressing the human hspa12b gene (Tg). Wild-type (WT) littermates served as controls. Tg and WT mice were treated with lipopolysaccharide (LPS) and cardiac function was measured after 6 h. LPS treatment caused cardiac dysfunction in WT mice. In contrast, cardiac function was significantly preserved in Tg mice following LPS administration. LPS increased the expression of vascular cell adhesion molecule-1 (VCAM-1)/intercellular adhesion molecule-1 (ICAM-1) and leucocyte infiltration into the myocardium of WT mice. In Tg mice, LPS-increased VCAM-1/ICAM-1 expression and leucocyte infiltration were significantly attenuated. Overexpression of HSPA12B also prevented the decrement in the activation of phosphatidlyinositide 3-kinase (PI3K)/protein kinase B (Akt) signalling in the myocardium. Importantly, PI3K inhibition with Wortmannin abolished the protection of HSPA12B against LPS-induced cardiac dysfunction. these results suggest that HSPA12B plays an important role in the attenuation of endotoxin-induced cardiac dysfunction and that the mechanisms involve the preserved activation of PI3K/Akt signalling, resulting in attenuation of LPS-increased expression of VCAM-1/ICAM-1 and leucocyte infiltration into the myocardium.