Zhenguo Zhao1, Wei Qu2, Kai Wang3, Sijin Chen4, Lijin Zhang5, Danlian Wu6, Zhigao Chen7. 1. Department of Hepatobiliary Surgery, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, 214400, People's Republic of China. Electronic address: jyzzguo@sina.com. 2. Department of Pharmacy, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, 214400, People's Republic of China. Electronic address: cpuquwei@163.com. 3. Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People's Republic of China. Electronic address: wkwhjy@163.com. 4. Department of Orthopedics, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, 214400, People's Republic of China. Electronic address: csj9036@126.com. 5. Department of Urinary Surgery, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, 214400, People's Republic of China. Electronic address: stzlj913729553@163.com. 6. Department of Pharmacy, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, 214400, People's Republic of China. Electronic address: wdl.603@126.com. 7. Department of Pharmacy, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, 214400, People's Republic of China. Electronic address: jychenzhigao@sina.com.
Abstract
AIMS: Bisphenol A (BPA) can induce intestinal epithelial cell barrier dysfunction; however, its effects on the intestinal mucus barrier remain unclear. We used LS174T cells as a model to investigate the effects of BPA on the functions of intestinal goblet cells. MAIN METHODS: This study used CCK-8, flow cytometry, ELISA and real-time PCR to investigate the effects of BPA on mitochondrial dynamics, oxidative stress and apoptosis in goblet cells. In addition, mucin synthesis and secretion were evaluated using PAS staining and a PAS assay, respectively. KEY FINDINGS: Our results indicate that BPA reduced cell viability in a time- and concentration-dependent manner. BPA induced mitochondrial dysfunction, as indicated by the depolarization of the mitochondrial membrane potential, inhibition of mitochondrial respiratory chain complex enzyme activity and reduction of ATP production. Moreover, BPA caused oxidative stress by significantly increasing the accumulation of ROS, as well as oxidative stress products, and reducing the antioxidant capacity. Furthermore, BPA induced intestinal goblet cell apoptosis, accompanied by increased DNA fragmentation, caspase-3, -8, -9,-10 gene expression and enzyme activity. Additionally, BPA inhibited the synthesis and secretion of mucin 2. SIGNIFICANCE: Our data suggest that BPA affected the secretory function of intestinal goblet cells by inducing mitochondrial dysfunction, oxidative stress, and apoptosis.
AIMS: Bisphenol A (BPA) can induce intestinal epithelial cell barrier dysfunction; however, its effects on the intestinal mucus barrier remain unclear. We used LS174T cells as a model to investigate the effects of BPA on the functions of intestinal goblet cells. MAIN METHODS: This study used CCK-8, flow cytometry, ELISA and real-time PCR to investigate the effects of BPA on mitochondrial dynamics, oxidative stress and apoptosis in goblet cells. In addition, mucin synthesis and secretion were evaluated using PAS staining and a PAS assay, respectively. KEY FINDINGS: Our results indicate that BPA reduced cell viability in a time- and concentration-dependent manner. BPA induced mitochondrial dysfunction, as indicated by the depolarization of the mitochondrial membrane potential, inhibition of mitochondrial respiratory chain complex enzyme activity and reduction of ATP production. Moreover, BPA caused oxidative stress by significantly increasing the accumulation of ROS, as well as oxidative stress products, and reducing the antioxidant capacity. Furthermore, BPA induced intestinal goblet cell apoptosis, accompanied by increased DNA fragmentation, caspase-3, -8, -9,-10 gene expression and enzyme activity. Additionally, BPA inhibited the synthesis and secretion of mucin 2. SIGNIFICANCE: Our data suggest that BPA affected the secretory function of intestinal goblet cells by inducing mitochondrial dysfunction, oxidative stress, and apoptosis.