ABSTRACT
The cornea is directly exposed to cigarette smoke, and smoking is a risk factor for several corneal diseases including dry eye syndrome. Currently, heated tobacco products (HTPs) are widely used as substitutes for cigarette smoking around the world. In the present study, we investigated the molecular mechanism(s) leading to cellular injury induced by cigarette smoke extract (CSE) or HTPs. Exposure to CSE perturbed the formation of tight junctions, leading to an increase in cell volume, a decrease in transepithelial electrical resistance (TER) in the human corneal epithelial cell-transformed (HCE-T) cell line. Moreover, CSE exposure induced both lipid peroxidation and ferrous [Fe(II)] ion accumulation in autolysosomal compartments. Interestingly, a cleaved form of ferritin appeared when HCE-T cells were incubated with CSE. This aberrant ferritin processing was suppressed by treatment with autophagy inhibitors. Furthermore, the CSE-induced cell death was suppressed by either ferrostatin-1 or deferoxamine (DFO). CSE exposure also promoted the expression of cytokines whereas DFO treatment inhibited the CSE-induced expression of these cytokines. Exposure to HTPs also induced both HCE-T cell death and cleaved ferritin accumulation in a concentration- and time-dependent manner. These results indicated that CSE or HTPs activated the ferroptosis signaling pathway, which contributed to corneal epithelial cell injury.
Subject(s)
Apoferritins/metabolism , Cigarette Smoking/metabolism , Cornea/metabolism , Ferritins/metabolism , Iron/metabolism , Oxidoreductases/metabolism , Cell Line , Cigarette Smoking/adverse effects , Cornea/cytology , Epithelial Cells/cytology , Epithelial Cells/metabolism , HumansABSTRACT
BACKGROUND/AIM: In spinal muscular atrophy (SMA), systemic deficiency of survival motor neurons (SMN) caused by loss or mutation of SMN1 leads to SMA symptoms. SMA was, for a long time, considered as a selective motor-neuron disease. However, accumulated evidence suggests that skeletal muscle cells are affected by low levels of SMN protein. The purpose of this study was to elucidate the function of SMN protein in skeletal cell differentiation and maturation. MATERIALS AND METHODS: In SMNΔ7 mice, which exhibit a systemic reduction of SMN protein, muscle atrophy was evaluated. To direct the effect of SMN against muscle cells, SMN functions were examined by knockdown of SMN in mouse myoblasts cell line C2C12 using siRNA. RESULTS: SMNΔ7 mice showed muscle atrophy accompanied by decreased both expression of a myogenesis marker and a proliferating marker. In SMN-knockdown myoblasts, early expression of myosin heavy chain and reduced multinuclear myotube formation were found. Decreased caspase-3 activity and reduced phosphorylation of Akt were observed at an early stage of differentiation in SMN-knockdown myoblasts. CONCLUSION: A critical role of SMN protein in muscle cell differentiation via caspase-3 and Akt activation was shown.
Subject(s)
Caspase 3 , Muscle Fibers, Skeletal , Proto-Oncogene Proteins c-akt , Survival of Motor Neuron 1 Protein/physiology , Animals , Caspase 3/genetics , Cell Differentiation , Disease Models, Animal , Mice , Muscle, Skeletal , Proto-Oncogene Proteins c-akt/geneticsABSTRACT
There are several animal models of glucocorticoid-induced osteoporosis (GIOP), but each requires a long time to evaluate drug effects. Zebrafish scales are classified as dermal bone and potentially represent a convenient animal model of GIOP because they rapidly regenerate following their removal. We clarified that dexamethasone-treated regenerating scales showed malformations, decreased size and circularity. Anti-osteoporosis drugs rescued the scale malformation phenotype eight-days following the removal of scales. Hence, the dexamethasone-induced regenerating scale malformation model may be a useful animal model for discovering drugs to treat GIOP.
