title: The restrained expression of NF-kB in renal tissue ameliorates folic acid induced acute kidney injury in mice.
abstract: The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI.
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh, India.
authors.forename: Dev
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh, India.
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Singla
authors.affiliation: Centre for Systems Biology & Bioinformatics, Panjab University, Chandigarh, India.
authors.forename: Veena
authors.initials: V
authors.lastname: Puri
authors.affiliation: Biotechnology Branch, University Institute of Engineering & Technology, Panjab University, Chandigarh, India; Centre for Stem Cell & Tissue Engineering, Panjab University, Chandigarh, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Puri
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005492:Folic Acid; D015870:Gene Expression; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007677:Kidney Function Tests; D008297:Male; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D011759:Pyrrolidines; C498144:Rela protein, mouse; D013859:Thiocarbamates; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; C020972:pyrrolidine dithiocarbamic acid; D005492:Folic Acid