Role of Fragile X Mental Retardation Protein in lung

Abstract

Lung is the organ of gaseous exchange. The epithelium of lung is exposed to inhaled air containing airborne pollutants, pathogens, particulate matters during the breathing process. Some of these chemicals are directly cytotoxic and some of them produce hazardous metabolic byproducts. Altogether these chemicals cause huge amount of redox burden on respiratory system. Lung epithelial cells must have unique repertoires to balance this redox burden or xenobiotic stress. In order understand the stress regulation in lung this study was initiated. newlineIntegrated stress response (ISR) is a major pathway for cellular stress management in lung. There are four upstream kinases, GCN2, PERK, PKR and HRI. In presence of stress stimuli like, amino acid starvation, protein misfolding, double stranded DNA break or oxidative stress these kinases become phosphorylated and activate eIF2and#945;. Activated or phosphorylated eIF2and#945; falls off from the translation machinery to stop global translation. The mRNAs are stored in stress granules during this process and some stress regulator genes are activated by a non-canonical translation machinery. ATF4 is such a master regulator which gets activated and activate many other downstream genes. newlineAccording to previous studies FMRP was established as a multifunctional protein that helps in regulation of oxidative and genotoxic stress in the cells from different origin. In absence of this protein more oxidative stress in murine brain, perturbed DNA damage response during replication stress and perturbed stress granule biogenesis were reported. These reports suggested that FMRP may have an important role in cellular stress response pathways. newlineExpression of FMRP in lung epithelium and indication of FMRP involvement in cellular stress response, led us to investigate the role of this protein in the stress response of lung and lung derived cells. newline newline