Neuron-Specific Enolase in Non-Neoplastic Lung Diseases, a Marker of Hypoxemia?

Abstract

Neuron-specific enolase (NSE) is a glycolytic enzyme localized within neuronal and neuroendocrine tissues. Serum NSE is widely used as a marker of neuroendocrine tumors. Moderate serum NSE elevation has been reported in some patients with benign lung diseases. We decided to investigate whether the elevation of serum NSE in non-neoplastic lung diseases is connected with hypoxemia and to what extent the recovery of sufficient ventilation with a respirator may influence NSE concentrations. Serum NSE was estimated by means of radioimmunoassay in 83 patients with various non-neoplastic lung diseases. Serum NSE exceeding 12.5 micrograms/L was significantly more frequent in patients with marked hypoxemia (PaO2 < 6.67 kPa; p = 0.03) than in others. The median NSE value in the group of patients without respiratory failure (Ro) was 7.2 micrograms/L (10% > 12.5 micrograms/L), in the group of patients with respiratory failure not requiring mechanical ventilation (Rf) it was 8.5 micrograms/L (24% > 12.5 micrograms/L), and in the group of patients with respiratory failure requiring mechanical ventilation (Rfv) 13.1 micrograms/L (60% > 12.5 micrograms/L). The differences between the Rfv group and the other two groups (Rf and Ro) were significant (P = 0.049 and p = 0.0004, respectively). During successful mechanical ventilation elevated serum NSE decreased to values below the cutoff in 8/10 patients. We conclude that serum NSE elevation is a frequent event in patients with terminal hypoxemia in the course of benign lung diseases. Normalization of serum NSE is observed in the majority of patients during the first week of mechanical ventilation.

Hypoxia induces a HIF-1α dependent signaling cascade to make a complex metabolic switch in SGBS-adipocytes

“…The most striking transcriptional induction in our data has been determined for ENO2, whose gene product converts phosphoglycerate to phophoenolpyruvate, with a fold change expression of 177. ENO2 has been known for a while to be inducible by hypoxia (Szturmowicz et al, 1998), and its upregulation has been determined in murine melanoma cells (Olbryt et al, 2006), human cord blood and bone marrow mesenchymal stem cells (Martin-Rendon et al, 2007), as well as in adipocytes (Mazzatti et al, 2012) but not to the extent as revealed by our data. In view of our binding site analysis and the striking transcriptional attenuation after HIF-1 inhibition we conclude that HIF-1α directly binds the ENO2 promoter and therefore is responsible for their mRNA upregulation in adipocytes.…”

Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes

“…It regulates the steady-state concentration of 2,6-bisphosphate, an allosteric activator of phosphofructokinase. Like PFKP and ENO2, it is activated by hypoxia as well [ 3 , 18 , 19 , 20 ]. In metabolic screens PFKFB4 has been proposed as a new potential target in cancer therapy as its silencing increased the ROS level and inhibited survival of cancer cells but not epithelial cells.…”

ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model

“…29 Expressions of nine of the upregulated genes, IGFBP-3, ADM, ANGPTL4, PLOD2, DSIPI, NDRG1, ENO2, HIG2 and BNIP3L, has been reported previously to be induced by hypoxia. 26,[29][30][31][32][33][34][35][36][37][38] We hypothesize that ZD6474 inhibits neovascularization in tumors, thereby limiting the oxygen and nutrient supply and resulting in tumor hypoxia and upregulation of hypoxia-inducible genes. If this hypothesis is correct, hypoxiaregulated genes and gene products might be useful biomarkers for the pharmacodynamic effects of ZD6474 and other antiangiogenic agents in preclinical and clinical settings.…”