A systematic review: on the mercaptoacid metabolites of acrylamide, N-acetyl-S-(2-carbamoylethyl)-L-cysteine.

Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs. We reviewed a total of 25 studies from eight countries. In the general population, urinary AAMA levels were higher in smokers than in non-smokers, and higher in children than in adults; the highest levels of AAMA were found in the population from Spain, compared with the general population from other countries. In addition, AAMA is associated with several diseases, especially cardiovascular system diseases. Therefore, AAMA, as a biomarker of internal human exposure, can reflect acrylamide intake in the short term, which is of great significance for tracing acrylamide-containing foods and setting the allowable intake of acrylamide in foods.

Stimulating the expression of sphingosine kinase 1 (SphK1) is beneficial to reduce acrylamide-induced nerve cell damage.

Sphingosine kinase 1 (SphK1) is an important signaling molecule for cell proliferation and survival. However, the role of SphK1 in acrylamide (ACR)-induced nerve injury remains unclear. The purpose of this study was to investigate the role and potential mechanism of SphK1 in ACR-induced nerve injury. Liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) and reverse transcription-quantitative PCR (RT-qPCR) were used to detect sphingosine 1-phosphate (S1P) content in serum and SphK1 content in whole blood from an occupational work group exposed to ACR compared to a non-exposed group. For in vitro experiments, SphK1 in human SH-SY5Y neuroblastoma cells was activated using SphK1-specific activator phorbol 12-myristate 13-acetate (PMA). Our research also utilized cell viability assays, flow cytometry, western blots, RT-qPCR and related protein detection to assess activity of the mitogen activated protein kinase (MAPK) signaling pathway. The results of the population study showed that the contents of SphK1 and S1P in the ACR-exposed occupational contact group were lower than in the non-exposed group. The results of in vitro experiments showed that expression of SphK1 decreased with the increase in ACR concentration. Activating SphK1 improved the survival rate of SH-SY5Y cells and decreased the apoptosis rate. Activating SphK1 in SH-SY5Y cells also regulated MAPK signaling, including enhancing the phosphorylation of extracellular signal-regulated protein kinases (ERK) and inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK) and p38. These results suggest that activating SphK1 can protect against nerve cell damage caused by ACR.

UNC5H4-induced apoptosis in non-small cell lung cancer is not dependent on p53 status only.

The aim of the present study was to investigate the expression profile and prognostic significance of uncoordinated 5 homolog 4 (UNC5H4) in patients with lung cancer and to evaluate whether UNC5H4 expression may serve as an index for radiosensitivity. UNC5H4 and p53 expression levels were detected by immunohistochemistry, apoptosis was determined by a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and caspase 3 activation was determined by western blotting. The results showed that UNC5H4 expression was largely located in the membrane of the normal bronchial epithelium, but absent in the membranous regions or ectopic cytoplasm of 80/130 (61.5%) non-small cell lung cancer (NSCLC) tissue samples. Abnormal UNC5H4 expression was demonstrated to correlate with the degree of differentiation (P=0.015), TNM staging (P=0.037). Cytoplasmic UNC5H4 expression was shown to correlate negatively with p53 mutant type (mt) expression (r=-0.270; P=0.002) and positively with the apoptotic index (r=0.254; P=0.004). The statistical analyses indicated that the prognosis of patients with normal UNC5H4 expression was improved compared with that of patients with abnormal UNC5H4 expression, however, no significant difference was identified (P=0.125). Exposure of NSCLC tissue samples to X-radiation increased UNC5H4 expression and caspase 3 activity significantly, irrespective of p53 mutation status. In conclusion, these results indicate that X-rays induce apoptosis via the p53 pathway, and when this pathway is compromised, an additional pathway is utilized.