mRNA Translation in Diabetic Nephropathy

Kasinath, Balakuntalam S.; Lee, Myung Ja; Féliers, Denis; Sonenberg, Nahum

doi:10.1007/978-1-59745-153-6_6

Cited by 3 publications

(3 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Free eIF4E binds to eIF4G and facilitates onset of the initiation phase of mRNA translation. Adapted from reference (117) these complexities in the 5ЈUTR and facilitates scanning to locate the AUG by the preinitiation complex. There is disagreement if helicase activity of eIF4A alone, without eIF4B, is sufficient because it may resolve complexities that are only four to five bases long (15).…”

Section: Initiation Phasementioning

confidence: 99%

mRNA Translation

Kasinath

Mariappan²,

Sataranatarajan³

et al. 2006

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Ambient protein levels are under coordinated control of transcription, mRNA translation, and degradation. Whereas transcription and degradation mechanisms have been studied in depth in renal science, the role of mRNA translation, the process by which peptide synthesis occurs according to the genetic code that is present in the mRNA, has not received much attention. mRNA translation occurs in three phases: Initiation, elongation, and termination. Each phase is controlled by unique eukaryotic factors. In the initiation phase, mRNA and ribosomal subunits are brought together. During the elongation phase, amino acids are added to the nascent peptide chain in accordance with codon sequences in the mRNA. During the termination phase, the fully synthesized peptide is released from the ribosome for posttranslational processing. Signaling pathways figure prominently in regulation of mRNA translation, particularly the phosphatidylinositol 3 kinase-Akt-mammalian target of rapamycin pathway, the AMP-activated protein kinase-tuberous sclerosis complex protein 1/tuberous sclerosis complex protein 2-Rheb pathway, and the extracellular signal-regulated kinase 1/2 type mitogen-activated protein kinase signaling pathway; there is significant cross-talk among these pathways. Regulation by mRNA translation is suggested when changes in mRNA and protein levels do not correlate and in the setting of rapid protein synthesis. Ongoing work suggests an important role for mRNA translation in compensatory renal growth, hypertrophy and extracellular matrix synthesis in diabetic nephropathy, growth factor synthesis by kidney cells, and glomerulonephritis. Considering that mRNA translation plays an important role in cell growth, development, malignancy, apoptosis, and response to stress, its study should provide novel insights in renal physiology and pathology.

show abstract

Section: Initiation Phasementioning

confidence: 99%

mRNA Translation

Kasinath

Mariappan²,

Sataranatarajan³

et al. 2006

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Regulation of gene expression culminating in protein synthesis is complex and tightly regulated consistent with the fundamental role of proteins as important executors of cell function [1]. While considerable attention has been paid to the regulation of transcription as a site of regulation of protein synthesis, our understanding of the role played by messenger RNA (mRNA) translation in this process is rudimentary.…”

Section: Introductionmentioning

confidence: 99%

“…The next step is helped by eEF2 which is active when dephosphorylated on Thr56. Dephosphorylated eEF2 is believed to facilitate movement of the ribosomal complex exactly three bases in the 5′ to 3′ direction such that the position of the aminoacyl tRNA now corresponds to the P site [1, 16]. At the P site, a peptide bond is created between the previous amino acid and the one that has arrived newly and releases tRNA from the previous amino acid.…”

Section: Introductionmentioning

confidence: 99%

Novel mechanisms of protein synthesis in diabetic nephropathy—role of mRNA translation

Kasinath

Mariappan

Sataranatarajan

et al. 2008

Rev Endocr Metab Disord

View full text Add to dashboard Cite

Ambient protein levels are affected by both synthesis and degradation. Synthesis of a protein is regulated by transcription and messenger RNA (mRNA) translation. Translation has emerged as an important site of regulation of protein expression during development and disease. It is under the control of distinct factors that regulate initiation, elongation and termination phases. Regulation of translation occurs via signaling reactions, guanosine diphosphate–guanosine triphosphate binding and by participation of non-coding RNA species such as microRNA. Recent work has revealed an important role for translation in hypertrophy, matrix protein synthesis, elaboration of growth factors in in vivo and in vitro models of diabetic nephropathy. Studies of translation dysregulation in diabetic nephropathy have enabled identification of novel therapeutic targets. Translation of mRNA is a fertile field for exploration in investigation of kidney disease.

show abstract

High Glucose, High Insulin, and Their Combination Rapidly Induce Laminin-β1 Synthesis by Regulation of mRNA Translation in Renal Epithelial Cells

et al. 2007

Self Cite

View full text Add to dashboard Cite

Laminin is a glycoprotein that contributes to renal extracellular matrix expansion in diabetes. We investigated regulation of laminin-␤1 synthesis in murine renal proximal tubular epithelial cells by 30 mmol/l glucose (high glucose), 1 nmol/l insulin (high insulin), and their combination (high glucose؉high insulin), simulating conditions observed during progression of type 2 diabetes. Compared with 5 mmol/l glucose and no insulin (control), high glucose alone, high insulin alone, or high glucose؉high insulin together increased laminin-␤1 chain protein synthesis within 5 min, lasting for up to 60 min with no change in laminin-␤1 mRNA levels. Cycloheximide, but not actinomycin-D, abrogated increased laminin-␤1 synthesis. High glucose, high insulin, and high glucose؉high insulin stimulated phosphorylation of 4E-BP1, a repressor binding protein for eukaryotic initiation factor 4E (eIF4E), that was dependent on activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin. High glucose, high insulin, and high glucose؉high insulin also promoted release of eIF4E from 4E-BP1, phosphorylation of eIF4E, and increase in eIF4E association with eIF4G, critical events in the initiation phase of mRNA translation. High glucose, high insulin, and high glucose؉high insulin increased Erk phosphorylation, which is an upstream regulator of eIF4E phosphorylation, and PD098059, which is a MEK inhibitor that blocks Erk activation, abolished laminin-␤1 synthesis. This is the first demonstration of rapid increment in laminin-␤1 synthesis by regulation of its mRNA translation by cells exposed to high glucose, high insulin, or high glucose؉high insulin. Diabetes 56:476 -485, 2007 I nsulin resistance and hyperinsulinemia are seen early in type 2 diabetes, followed by hyperglycemia, sometimes accompanied by continued elevation of plasma insulin, although insufficient to compensate for metabolic demands (1,2). Whereas the role of hyperglycemia in diabetes-related complications is established, the role of insulin remains unclear. Resistance to insulin actions in tissues in type 2 diabetes is not universal, with kidney and retina remaining sensitive in contrast to liver (3,4). Insulin may have a regulatory role in renal extracellular matrix (ECM) synthesis because renal cortical insulin receptor activation (3) coincides with the onset of accumulation of laminin-␤1, an abundant constituent of the renal ECM (5).Progressive accumulation of ECM proteins in the glomerular mesangium and tubulointerstitium in diabetes involves laminin in addition to type IV collagen and fibronectin (5-7). Laminin is a large heterotrimeric glycoprotein consisting of ␣-, ␤-, and ␥-chains, with the subunit composition varying with compartment of the renal ECM. Thus, the glomerular basement membrane contains ␣5-, ␤2-, and ␥1-chains, whereas the tubular basement membrane contains ␣5/1-, ␤1-, and ␥1-chains (8). Laminin is involved in regulation of glomerular barrier function because mice lacking laminin-␤2 develop severe proteinuria (9). Renal laminin-...

show abstract

mRNA Translation in Diabetic Nephropathy

Cited by 3 publications

References 122 publications

mRNA Translation

mRNA Translation

Novel mechanisms of protein synthesis in diabetic nephropathy—role of mRNA translation

High Glucose, High Insulin, and Their Combination Rapidly Induce Laminin-β1 Synthesis by Regulation of mRNA Translation in Renal Epithelial Cells

Contact Info

Product

Resources

About