role of hdac2 p gp and mrp 1 in steroid resistance in childhood ns

Abstract

newline NS (NS) is one of the most common chronic glomerular disorders characterized newlineby alteration in permeability of capillary of glomeruli, resulting in the excessive loss of newlineproteins in urine. NS patients are clinically characterized by edema, hypoalbuminemia newline(less than 2.5g/dL) and proteinuria greater than 40 mg /m2/h. As compared to adults, newlinechildren suffer from NS of unknown etiology. The International Study of Kidney newlineDisease in Children (ISKDC) established the standard initial treatment of idiopathic NS newlineas 4 weeks of daily steroids . The NS patients on steroid are broadly categorized into newlinetwo groups; steroid-sensitive NS (SSNS) and steroid- resistant NS (SRNS). There are newlinemany theories that support that immune system plays a vibrant role in the pathogenesis newlineof NS, expression of T lymphocytes had been showed to be altered in SRNS patients as newlinecompared to SSNS patients. Steroids are the mainstay therapy for NS patients for many newlineyears. It can counter inflammatory cytokines signaling. Once inside the cell steroids newlinebind to glucocorticoid receptor and exert its immunosuppressive effect by two newlinepathways. Firstly, the cortisol-glucocorticoid receptor moves inside the nucleus, were it newlinebinds to glucocorticoid-responsive elements (GRE) and up-regulates the expression of newlineanti-inflammatory cytokines. Secondly, down-regulation of pro-inflammatory newlinetranscription factors, such as nuclear factor-and#954;B complex. The adequate bioavailability of newlinesteroids inside the cell is necessary to suppress the inflammatory genes expression. newlineUnder the condition of xenobiotics stress, cells may upregulate the expression of two newlinemajor types of efflux pumps, P-glycoprotein (P-gp) and multidrug resistance-associated newlineprotein 1 (MRP-1). P-gp is a 170-kD product coded by multidrug resistance-1 (MDR-1) newlinegene which belongs to the ATP binding cassette superfamily of transportproteins. newlineHistone acetylases (HATs) and histone deacetylases (HDACs) are two classes of newlineenzyme that tightly regulates the transcription of any gene in the nucleus. HATs first newlineacetyl