Dietary regulation of ruminal bovine UT-B urea transporter expression and localization

Simmons, Nicholas L.; Chaudhry, AS; Graham, Christopher; Scriven, E; Thistlethwaite, Angela; Smith, Craig P.; Stewart, Gavin

doi:10.2527/jas.2008-1710

Cited by 58 publications

(77 citation statements)

References 30 publications

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“…Urea transporter expression is known to respond directly to nitrogen and urea load (33,34) and mediates the facilitated diffusion of urea down its concentration gradient (35,36). The altered expression of SLC14A1 transcript/UTB protein is therefore likely to be a direct response to the elevated brain urea we observed in HD.…”

Section: Discussionmentioning

confidence: 94%

Brain urea increase is an early Huntington’s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases

Handley

Reid

Bräuning

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73-line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.is a dominantly inherited neurological disorder typified by chorea, psychological disturbance, and dementia. The symptoms progress and result in premature death, typically 10-15 y after onset. Currently no available treatment can delay or prevent the onset of HD. The gene responsible, Huntingtin (HTT), is ubiquitously expressed and encodes the large and multifunctional huntingtin protein.The disease-causing mutation is an expanded CAG repeat in exon 1 of HTT, coding for a glutamine tract within the protein (1). The disease-causing repeat lower length threshold is 36 units and is fully penetrant at 40 units and above (2, 3). There is an inverse correlation between expanded CAG repeat size and age at onset of symptoms (4-6). Although the mutation is well defined, the pathogenic process is not sufficiently understood to enable effective treatment. The majority of HD research focuses on the brain where there is characteristic neuropathology, primarily atrophy of the striatum (7).Alongside the striking neurological phenotype of HD, there is a generalized metabolic disruption. HD mutation carriers weigh less on average than non-HD individuals (8). Weight loss begins presymptomatically (9, 10), and in symptomatic individuals, energy expenditure far exceeds that utilized in movement, despite high calor...

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Section: Discussionmentioning

confidence: 94%

Brain urea increase is an early Huntington’s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases

Handley

Reid

Bräuning

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…AQP3 can also moderately permeate urea although to a lesser extent [1] and this function might also play a role in volume regulation in hRBC. As for bRBC, besides a high expression level of the facilitated urea transporter [34] coexistent with urea permeability similar to the human specie [28], which itself may improve erythrocyte osmotic fragility, the physiological reasoning for the absence of a glycerol transporter remains ambiguous. …”

Section: Discussionmentioning

confidence: 99%

Lack of Aquaporin 3 in bovine erythrocyte membranes correlates with low glycerol permeation

Campos

Moura

Oliva

et al. 2011

Biochemical and Biophysical Research Communications

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In general, erythrocytes are highly permeable to water, urea and glycerol.However, expression of aquaporin isoforms in erythrocytes appears to be species characteristic. In the present study, human (hRBC) and bovine (bRBC) erythrocytes were chosen for comparative studies due to their significant difference in membrane glycerol permeability.Osmotic water permeability (P f ) at 23 ºC was (2.89 0.37) 10 -2 and (5.12 0.61) 10 -2 cm s -1 for human and bovine cells respectively, with similar activation energies for water transport. Glycerol permeability (P gly ) for human ((1.37 0.26) 10 -5 cm s -1 ) differed in three orders of magnitude from bovine erythrocytes ((5.82 0.37) 10 -8 cm s -1 ) that also showed higher activation energy for glycerol transport.When compared to human, bovine erythrocytes showed a similar expression pattern of AQP1 glycosylated forms on immunoblot analysis, though in slight higher levels, which could be correlated with the 1.5-fold larger P f found. However, AQP3 expression was not detectable. Immunofluorescence analysis confirmed the absence of AQP3 expression in bovine erythrocyte membranes.In conclusion, lack of AQP3 in bovine erythrocytes points to the lipid pathway as responsible for glycerol permeation and explains the low glycerol permeability and high E a for transport observed in ruminants.

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“…The surface of the reticulum is enlarged by a network-like system of ridges, which may serve to separate material, but which also increases the surface area. The surface of the rumen is coated by numerous papillae, the length of which greatly increases in response to dietary challenges (Gä bel et al, 1987;Simmons et al, 2009), thus showing a clear correlation with absorptive function. Omasal papillae are smaller, but macroscopic inspection of the organ shows an exquisite anatomy with multiple leaflets, between which ingesta with a high dry matter (DM) content can be found.…”

Section: Anatomy and Histology Of The Forestomachsmentioning

confidence: 99%

Transport of cations and anions across forestomach epithelia: conclusions from in vitro studies

Leonhard-Marek

Stumpff

Martens

2010

Animal

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Secretion of saliva as well as absorptive and secretory processes across forestomach epithelia ensures an optimal environment for microbial digestion in the forestomachs. Daily salivary secretion of sodium (Na 1 ) exceeds the amount found in plasma by a factor of 2 to 3, while the secretion of bicarbonate (HCO 3 2 ) is 6 to 8 times higher than the amount of HCO 3 2 in the total extracellular space. This implies a need for efficient absorptive mechanisms across forestomach epithelia to allow for an early recycling. While Na 1 is absorbed from all forestomachs via Na 1 /H 1 exchange and a non-selective cation channel that shows increased conductance at low concentrations of Mg 21 , Ca 21 or H 1 in the luminal microclima and at low intracellular Mg 21 , HCO 3 2 is secreted by the rumen for the buffering of ingesta but absorbed by the omasum to prevent liberation of CO 2 in the abomasum. Fermentation provides short chain fatty acids and ammonia (NH 3 ) that have to be absorbed both to meet nutrient requirements and maintain ruminal homeostasis of pH and osmolarity. The rumen is an important location for the absorption of essential minerals such as Mg 21 from the diet. Other ions can be absorbed, if delivered in sufficient amounts (Ca 21 , P i , K 1 , Cl 2 and NH 4 1 ). Although the presence of transport mechanisms for these electrolytes has been described earlier, our knowledge about their nature, regulation and crosstalk has increased greatly in the last years. New transport pathways have recently been added to our picture of epithelial transport across rumen and omasum, including an apical non-selective cation conductance, a basolateral anion conductance, an apical H 1 -ATPase, differently expressed anion exchangers and monocarboxylate transporters.Keywords: ruminants, sodium potassium magnesium and calcium, short chain fatty acids, chloride and bicarbonate, channels transporters and exchangers ImplicationsThe improved knowledge of ruminal ion transport clearly underlines its physiological meaning for the whole animal. For example, magnesium absorption is markedly reduced at low Mg and high K intake and the effect of potassium is diminished at high Mg intake. This variable interaction has been quantified recently permitting the prediction of Mg absorption. Great progress has also been made in understanding the interactions between the absorptive pathways for Na, short chain fatty acids and ammonium. The new findings on structure and regulation of various ion transporters will allow a better understanding of the challenges that different diets pose to the maintenance of homeostatic conditions within the rumen and within the cells of the surrounding epithelium, with the implications for the investigation of ruminal adaptation to different diets. Future studies on transport pathways should include the barrier function of rumen epithelium and its possible impairment under harsh feeding conditions.

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Dietary regulation of ruminal bovine UT-B urea transporter expression and localization

Cited by 58 publications

References 30 publications

Brain urea increase is an early Huntington’s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases

Brain urea increase is an early Huntington’s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases

Lack of Aquaporin 3 in bovine erythrocyte membranes correlates with low glycerol permeation

Transport of cations and anions across forestomach epithelia: conclusions from in vitro studies

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