BACKGROUND: Formaldehyde (FA) is associated with the occurrence of leukemia, and oxidative stress is considered to be a major reason. As an endogenous biomarker of oxidative stress, few studies focus on the relationship between peroxiredoxin III (PrxIII) and FA toxicity. Our previous research observed high expression of PrxIII occurred in the process of apoptosis of bone marrow cells (BMCs) induced by FA, however the exact mechanism is unclear. Therefore, this paper aimed to explore the possible association between FA toxicity and PrxIII gene.
METHODS: We first, used a Cell Counting Kit-8 (CCK-8) to detect the viability of BMCs after they were exposed to different doses of FA (50, 100, 200 μmol/L) for different exposure time (12, 24, 48 h), then chose 24 h as an exposure time to detect the expression of PrxIII for exposing different doses of FA by Quantitative reverse transcription-PCR (qRT-PCR) and Western blot analysis. Based on our preliminary experimental results, we chose 100 μmol/L FA as an exposure dose to expose for 24 h, and used a small interfering RNA (siRNA) to silenced PrxIII to examine the cell viability by CCK-8, reactive oxygen species (ROS) level by DCFH-DA, apoptosis by Annexin V/PI double staining and cell cycle by flow cytometry (FCM) so as to explore the possible regulatory effect of PrxIII silencing on FA-induced bone marrow toxicity.
RESULTS: High expression of PrxIII occurred in the process of FA-induced oxidative stress. Silencing of PrxIII prevented FA from inducing oxidative stress, thus increasing cell viability, decreasing ROS level, rescuing G0 -G1 and G2 -M arrest, and reducing cell apoptosis.
CONCLUSIONS: PrxIII silencing might be a potential target for alleviating FA-induced oxidative damage.

MicroRNAs (miRNAs) are small RNAs that regulate target gene expression. Using microarray-based miRNA expression profiling, we compared the miRNA expression in granulocytes from four patients with acute myeloid leukemia and four healthy controls. Thirty-four miRNAs were found to be differentially expressed, including 20 miRNAs that were up-regulated and 14 miRNAs that were down-regulated. The expression of selected miRNAs (miR-26a-5p and miR-23b-3p) was independently validated in 20 patients and 12 healthy controls. Notably, we demonstrated that peroxiredoxin III (PrxIII) is a common direct target of both miR-26a-5p and miR-23b-3p. Furthermore, these results indicate that the two decreased miRNAs could scavenge cellular reactive oxygen species (ROS) by targeting the PrxIII gene. These findings are discussed with regard to the known function of PrxIII as a ROS scavenger and the high endogenous ROS levels required for hematopoietic stem cell differentiation. These findings may potentially offer insights into the pathological relationships between miR-26a-5p, miR-23b-3p and leukemogenesis.

In addition to the well-known effects of vitamin D (VitD) in maintaining bone health, there is increasing appreciation that this vitamin may serve important roles in other organs and tissues, including the brain. Given that VitD deficiency is especially widespread among the elderly, it is important to understand how the range of serum VitD levels that mimic those found in humans (from low to high) affects the brain during aging from middle age to old age. To address this issue, 27 male F344 rats were split into three groups and fed isocaloric diets containing low (100 IU/kg food), control (1000 IU/kg food), or high (10,000 IU/kg food) VitD beginning at middle age (12 months) and continued for a period of 4-5 months. We compared the effects of these dietary VitD manipulations on oxidative and nitrosative stress measures in posterior brain cortices. The low-VitD group showed global elevation of 3-nitrotyrosine compared to control and high-VitD-treated groups. Further investigation showed that this elevation may involve dysregulation of the nuclear factor κ-light-chain enhancer of activated B cells (NF-κB) pathway and NF-κB-mediated transcription of inducible nitric oxide synthase (iNOS) as indicated by translocation of NF-κB to the nucleus and elevation of iNOS levels. Proteomics techniques were used to provide insight into potential mechanisms underlying these effects. Several brain proteins were found at significantly elevated levels in the low-VitD group compared to the control and high-VitD groups. Three of these proteins, 6-phosphofructokinase, triose phosphate isomerase, and pyruvate kinase, are involved directly in glycolysis. Two others, peroxiredoxin-3 and DJ-1/PARK7, have peroxidase activity and are found in mitochondria. Peptidyl-prolyl cis-trans isomerase A (cyclophilin A) has been shown to have multiple roles, including protein folding, regulation of protein kinases and phosphatases, immunoregulation, cell signaling, and redox status. Together, these results suggest that dietary VitD deficiency contributes to significant nitrosative stress in brain and may promote cognitive decline in middle-aged and elderly adults.