Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of uremia-induced chronic acidosis on fractional protein synthesis rate (FSR), degradation (FDR) and protein tissue growth (FRG) in skeletal muscle were examined in young rats fed a 30% protein diet. This diet induced acidosis in UA rats, which was corrected by NaHCO3 supplementation in UB rats. Blood pH and plasma HCO3- were 7.22 +/- 0.01 and 15.2 +/- 0.8 mmol/l in UA rats vs. 7.41 +/- 0.01 and 25.8 +/- 0.9 in UB rats. Both UA and UB groups had similar renal function and food intake. Acidosis impaired weight gain (4.0 +/- 0.3 vs. 5.0 +/- 0.4 g/day, p < 0.05) and length gain (0.31 +/- 0.02 vs. 0.42 +/- 0.02 cm/day, p < 0.001). UA and UB rats showed similar muscle FSR (10.4 +/- 0.5 vs. 10.8 +/- 0.5%/day) and RNA content (6.3 +/- 0.2 vs. 6.2 +/- 0.2 micrograms/g protein). UA rats had lower FGR than UB rats (3.9 +/- 0.8 vs. 5.9 +/- 0.6%/day, p < 0.05). Therefore, muscle FDR was increased in UA rats (6.30 +/- 0.99 vs. 5.10 +/- 0.7%/day).
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PMID:Protein synthesis and growth in uremic rats with and without chronic metabolic acidosis. 146 69

Absidiosis was produced experimentally in rabbits by intravenous inoculation of 1.4 x 10(5) spores of Absidia corymbifera. Infected rabbits exhibited a rise in body temperature, anorexia, dullness, listlessness, diarrhoea, occasional blindness, convulsions and death in some cases. Mortality occurred mainly between 6 to 9 days post infection (DPI) and overall mortality was 50 per cent during the three week observation period. No significant difference was observed in erythrocytic indices viz., Hb, PCV, TEC in control and infected rabbits. However, erythrocyte sedimentation rate was considerably increased in the infected rabbits. A state of leucocytosis was observed in the infected rabbits, which was due to increase in the relative percentage of neutrophils and decrease in lymphocytes. There was a significant increase in blood urea nitrogen concentrations of infected rabbits from 3 to 14 DPI as compared to controls, but serum creatinine values were not significantly altered at any stage of infection. The cause of death was attributed to kidney failure and uraemia in infected rabbits. The rabbit was found to be a suitable model for the study of absidiosis.
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PMID:Experimental Absidia corymbifera infection in rabbits: clinicopathological studies. 881 36

Resistance to growth hormone (GH) is a significant complication of advanced chronic renal failure. Thus while the circulating GH levels are normal or even elevated in uremia, resistance to the hormone leads to stunting of body growth in children and contributes to muscle wasting in adults. Insensitivity to GH is the consequence of multiple defects in the GH/insulin-like growth factor-1 (IGF-1) system. Expression of the GH receptor may be reduced, although this is not a consistent finding, GH activation of the Janus kinase 2-signal transducer (JAK2) and activator of transcription (STAT) signal transduction pathway is depressed and this leads to reduced IGF-1 expression, and finally there is resistance to IGF-1, a major mediator of GH action. We review these various defects with an emphasis on the GH-activated JAK2-STAT5 pathway, since this pathway is essential for normal body growth and there has been recent progress in our understanding of the perturbations that occur in uremia.
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PMID:Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling. 1569 35

Parathyroid (PT) hyperplasia is a major feature of secondary hyperparathyroidism (SH) in uremia. The transforming growth factor-alpha (TGFalpha) / epidermal growth factor receptor (EGFR)Ethgrowth loop is the main contributor to uremia-induced PT hyperplasia. Since integrin beta1 and focal adhesion kinase (FAK) are known to directly activate cell growth and enhance EGFR-driven growth, these studies examined their contribution to PT hyperplasia in uremia. Western blot analysis was used to measure the expression of EGFR, integrin beta1, and the non-receptor integrin-sensitive FAK, in PT glands from 8 hemodialysis patients with various degrees of SH at the time of the surgery, and in a normal human PT gland. In all patients, PT EGFR expression was higher than in the normal control. Integrin beta1, a direct activator of EGFR-driven growth, was increased in 5 of the 8 hyperplastic glands, whereas 7 out of 8 PT glands showed a marked enhancement in FAK expression, an elevation unrelated to increases in integrin beta1, but directly associated to time in hemodialysis. Similar increases in PT FAK content were observed after 1 month after the onset of uremia by 5/6 nephrectomy in rats. These findings suggest that in kidney disease, the increased PT cell growth driven by enhanced EGFR could be further aggravated through elevations in integrin beta1 and FAK expression.
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PMID:A role for enhanced integrin and FAK expression in uremia-induced parathyroid hyperplasia. 1751 28

Collagen type I is an abundant component of the extracellular matrix and due to its longevity, constitutes a prominent target of non-enzymatic post-translational in vivo modifications such as carbamylation and glycation. These protein modifications involved in aging, renal diseases and diabetes, are linked to elevated cancer risk. In this in vitro study, we investigated the impact of carbamylated and glycated collagen type I on the migratory behavior of the highly invasive HT1080 human fibrosarcoma cells. The proliferation of HT1080 on modified collagens did not differ from that on native form. The glycated collagen delayed the cell adhesion time whereas the carbamylated one had no effect. The migration ability of HT1080 was studied by quantifying single cell speed using videomicroscopy. Glycation strongly inhibited mean cell speed by 47% whereas carbamylation moderately affected it by 12%. In addition, the influence of these collagen modifications on actin and vinculin organization was studied. On the glycated collagen, 63% of cells revealed a dramatic loss of actin stress fibers vs. 28% on the carbamylated one. In these cells, disorganized F-actin was accompanied with a disturbance of vinculin and both proteins were localized at the rim of the cells. Concerning the focal adhesion kinase (FAK) expression, glycated collagen only induced a significant inhibition. Whereas, both collagen modifications provoked a differential inhibition of FAK phosphorylation state by 25% for carbamylation and 60% for glycation. In conclusion, our data suggest that, in vivo, collagen glycation and carbamylation may affect tumor cell metastasis. This suggestion is supported by clinical studies reporting less aggressive tumors in diabetic or uremic patients. Consequently, the impact of such post-translational modifications has to be taken into account in order to better understand the link between aging, diabetes or uremia and cancer progression.
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PMID:Impact of carbamylation and glycation of collagen type I on migration of HT1080 human fibrosarcoma cells. 2237 40