Recent evidence has demonstrated an appreciable expression of metallothionein (MT) in erythrocytes. However, the induction of the MT protein by hematopoietic growth factors and its subsequent functional significance on clonal expansion or differentiation of erythroid progenitor cells remain elusive. We therefore examined the effects of growth factors erythropoietin (EPO), granulocyte-monocyte colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3) on MT gene expression in erythroid progenitor K562 cell line. EPO, but not IL-3 or GM-CSF, induced a 3-fold increase in MT transcripts in K562 cells. MT induction was associated with EPO-induced cellular proliferation, suggesting a specific role for MT induction by EPO in erythroid progenitor cells. However, EPO- or sodium butyrate-induced differentiation as monitored by hemoglobin formation was inhibited in K562 cells stably transfected with an expression vector containing human MT-IIA gene. This inhibition of differentiation was partially reversed in these cells by an MT antisense phosphorothioate oligonucleotide. Furthermore, the MT-induced inhibition of differentiation was associated with downregulation of EPO receptor transcripts in K562 cells. These data suggest that, among growth factors required for erythropoiesis, EPO is a potent inducer of MT, and that MT may plays a significant role in EPO-induced proliferation, but not in the erythroid-specific differentiation of the progenitor cells.
Background/Aims: Cigarette smoke exposure (CSE) during pregnancy is a well-recognized health hazard that causes placental damage. Hydrogen sulfide (H2S) has been reported to protect multiple organs from injury. However, the protective effects of H2S have not been tested in the placenta. This study aimed to explore the potential of H2S in protecting placenta against oxidative injury induced by CSE during pregnancy and the possible underlying mechanisms. Methods: Pregnant SD rats were randomly divided into 4 groups: NaCl, NaHS (a donor of H2S), CSE and CSE+NaHS. Placental oxidative damage was detected by 8-hydroxy-2-deoxyguanosine (8-OHdG) stain and malondialdehyde (MDA) assay. Placental redox status was assessed by measuring reactive oxygen species (ROS), total antioxidant capacity (T-AOC) and glutathione (GSH) levels, as well as copper/zinc SOD (SOD1), manganese SOD (SOD2), catalase (CAT) and glutathione peroxidase (GPx) activities and expressions. Meanwhile, nuclear factor erythroid 2-related factor 2 (Nrf2) was analyzed by immunohistochemistry, real-time PCR and Western blot. Results: We found that NaHS markedly reduced the elevated levels of 8-OHdG and MDA induced by CSE. Further, NaHS treatment effectively mitigated CSE-induced placental redox imbalance by inhibiting ROS production, restoring T-AOC level, increasing GSH/GSSG ratio, and augmenting SOD1 SOD2, CAT and GPx activities and expressions. More notably, NaHS administration also reversed the aberrant decrease of Nrf2 due to CSE in rat placentas. Conclusion: Our data demonstrate that H2S can protect against CSE-induced placental oxidative damage probably by alleviating redox imbalance via Nrf2 pathway.
In this study, we implanted Schwann cells (SCs) transfected with Neuregulin 1 (NRG1) gene into rats with hemisection spinal cord injury, determined its effects on the repair of spinal cord injury and investigated the underlying mechanisms. Primary SCs were cultured, purified, and transfected with NRG1 gene. SCs and SCs transfected with NRG1 gene were implanted, respectively, into rats with hemisection spinal cord injury. Behavior, imaging, electrophysiology, and immuno-histological analyses were performed to evaluate the effect of NRG1 gene-transfected SCs on the repair of spinal cord injury. In vitro studies showed that NRG1 protein was highly expressed in SCs transfected with NRG1 gene. In addition, the receptors for NRG1, ErbB2, and ErbB4, were upregulated in a time-dependent manner. NRG1-transfected SCs secreted large amount of NRG1 proteins in vivo, which efficiently promoted the expression of ErbB2 and ErbB4 in the neurons and neuroglia cells. Moreover, the number of NSE-and GFAP-positive cells was increased. After cell transplantation, many transplanted cells survived and migrated to the areas with spinal cord injuries. The injuries were recovered in all the experimental groups, but the most significant recovery was observed in the group of rats implanted with SCs transfected with NRG1 gene. We conclude that NRG1-transfected SCs can significantly increase the effect on the repair of spinal cord injury. This repair effect is achieved via the upregulation of ErbB receptor in the target cells, increased proliferation of glial cells, and protection of neurons from apoptosis. Anat Rec, 293:1933Rec, 293: -1946
It has been postulated that prenatal cigarette smoke exposure (CSE) increases the risk for sudden infant death syndrome. The victims of infant death syndrome suffer from respiratory abnormalities, such as central apnea, diminished chemoreflex and alteration in respiratory pattern during sleep. However, no experimental evidence on CSE model exists to confirm whether prenatal CSE gives rise to reduction of neonatal central chemoreception in in vitro preparations in absence of peripheral sensory feedback. The aim of the present study was to test the hypothesis that maternal CSE during pregnancy depresses central chemoreception of the neonatal rats. The pregnant rats were divided into two groups, control (n = 8) and CSE (n = 8). Experiments were performed on neonatal (0–3days) rat pups. Fictive respiratory activity was monitored by recording the rhythmic discharge from the hypoglossal rootlets of the medullary slices obtained from the neonatal rats. The burst frequency (BF) and integrated amplitude (IA) of the discharge were analyzed. Their responses to acidified artificial cerebrospinal fluid (aCSF) were tested to indicate the change of the central chemosensitivity. Under condition of perfusing with standard aCSF (pH 7.4), no significant difference was detected between the two groups in either BF or IA (P>0.05). Under condition of perfusing with acidified aCSF (pH 7.0), BF was increased and IA was decreased in both groups (P<0.01). However, their change rates in the CSE group were obviously smaller than that in the control group, 66.98 ± 10.11% vs. 143.75 ± 15.41% for BF and −22.38 ± 2.51% vs. −44.90 ± 3.92% for IA (P<0.01). In conclusion, these observations, in a prenatal CSE model, provide important evidence that maternal smoking during pregnancy exerts adverse effects on central chemoreception of neonates.
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