Synergetic Effect of a-Lipoic Acid with Keratinocyte Growth Factor on Protecting Alveolar Epithelial Type II Cells of Rat Fetus from Hyperoxia -Induced Injury

Abstract

Aim: To explore the potential mechanism of the synergetic effect of α-lipoic acid with keratinocyte growth factor (KGF) on protecting alveolar epithelial type II cells (ATIICs) from hyperoxia-induced injury. Methods: Primary culture of ATIICs from the Sprague-Dawley rat fetuses was examined under room air and 95% of O₂. Various KGF concentrations (0 to 100 ng/mL) and 0.5 mM of α-lipoic were added into the cell culture. Levels of intracellular reactive oxygen species, necrosis, and proliferation of ATIICs were measured using flow cytometry, ELISA, and MTT assays, respectively. RT-PCR was performed to detect KGFR mRNA expression. Western blot was employed to detect the expression of KGFR, phospho-p53, HDAC1, and acetylated H3 and H4. Results: KGF promoted the proliferation and inhibited the apoptosis of ATIICs in room air or under temporary exposure to hyperoxia. However, the resistance of ATIICs to KGF was observed after prolonged exposure. Further investigation demonstrated that down-regulation of KGF receptor via activation of p53 and recruitment of HDAC1 induced by oxidative stress contributed to KGF resistance. This resistance could be attenuated by α-lipoic acid, a powerful antioxidant. Conclusion: Application of KGF combined with α-lipoic acid could inhibit KGF resistance to provide maximum protection to ATIICs from hyperoxic injury.

Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts

“…The well-studied pulmonary toxicity of hyperoxic gas is known to involve apoptotic cell death of alveolar epithelial cells (26), but exposure of the cell line IMR90 to a high oxygen concentration that is often administered to premature neonates (95% O2) did not increase a marker of apoptotic cell death in these fetal human lung fibroblasts (caspase 9, Figure 1). Although the 95% oxygen did cause a very minor increase in necrotic cells (<1% see Table 1), it seems unlikely that this small but statistically significant effect would have physiologic significance.…”

Regulation of the angiotensin II-p22phox-reactive oxygen species signaling pathway, apoptosis and 8-oxoguanine-DNA glycosylase 1 retrieval in hyperoxia-induced lung injury and fibrosis in rats

“…ROS induce endothelial dysfunction, cardiovascular and renal remodeling, inflammation and fibrosis. Previous studies have shown that AngII is closely associated with fibrosis in multiple organs (4,5). As pulmonary fibrosis results in a severe prognosis for newborns after hyperoxic treatment, AngII-induced ROS are thought to be a factor that should be considered in relation to the formation of pulmonary fibrosis (6,7).…”

“…Thus, hyperoxia-induced lung injury occurs, which is represented by pulmonary fibrosis. Therefore, neonates continue to require mechanical ventilation and oxygen therapy after their primary diseases have improved (3,4). …”

Thioredoxin‐1 Protects Bone Marrow‐Derived Mesenchymal Stromal Cells from Hyperoxia‐Induced Injury In Vitro

“…Cells were seeded into 6-, 24-, or 96-well cell culture plates overnight. The next day, cells were placed in hyperoxia (80% O 2 , 5% CO 2 ) or normoxic (21% O 2 , 5% CO 2 ) environment as previously described [ 20 , 25 , 26 ]. The concentration of O 2 was monitored in real time with a digital oxygen monitor (Hengaode, Beijing, China).…”