Osmolytes Offset the Urea’s Effect on Protein Structure and Function

Rahman, Safikur; Park, Jihyun; Kim, Jihoe

doi:10.1007/978-981-10-3707-8_4

Cited by 2 publications

(3 citation statements)

References 120 publications

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“…In this aspect, it serves as one of the osmolytes that aids in the maintenance of the hyperosmotic environment in the renal medulla interstitium [26,27]. The cells of the renal medulla also contain high concentrations of osmolytes like myo-inositol, i.e., organic osmolytes produced by the cells in order to tolerate great osmotic gradients without affecting intracellular protein functions as it is the case with high ionic strength [3,28]. Therefore, the cells of the renal medulla are the best model to study the effects of osmolytes in cell volume regulation since tolerance to steep changes in the extracellular osmolality is an integral part of their homeostasis.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Isotonic Activation of Cell Volume Regulation in Rat Peritoneal Mesothelial Cells and in Kidney Outer Medullary Collecting Duct Principal Cells

et al. 2021

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In disease states, mesothelial cells are exposed to variable osmotic conditions, with high osmotic stress exerted by peritoneal dialysis (PD) fluids. They contain unphysiologically high concentrations of glucose and result in major peritoneal membrane transformation and PD function loss. The effects of isotonic entry of urea and myo-inositol in hypertonic (380 mOsm/kg) medium on the cell volume of primary cultures of rat peritoneal mesothelial cells and rat kidney outer medullary collecting duct (OMCD) principal cells were studied. In hypertonic medium, rat peritoneal mesothelial cells activated a different mechanism of cell volume regulation in the presence of isotonic urea (100 mM) in comparison to rat kidney OMCD principal cells. In kidney OMCD cells inflow of urea into the shrunken cell results in restoration of cell volume. In the shrunken peritoneal mesothelial cells, isotonic urea inflow caused a small volume increase and activated regulatory volume decrease (RVD). Isotonic myo-inositol activated RVD in hypertonic medium in both cell types. Isotonic application of both osmolytes caused a sharp increase of intracellular calcium both in peritoneal mesothelial cells and in kidney OMCD principal cells. In conclusion, peritoneal mesothelial cells exhibit RVD mechanisms when challenged with myo-inositol and urea under hyperosmolar isotonic switch from mannitol through involvement of calcium-dependent control. Myo-inositol effects were identical with the ones in OMCD principal cells whereas urea effects in OMCD principal cells led to no RVD induction.

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Section: Discussionmentioning

confidence: 99%

“…During persistent hyperosmolar conditions, the inorganic ions need to be replaced by compatible electrically neutral organic osmolytes that do not disturb protein function [1]. Urea and inositol could be identified as important electroneutral organic osmolytes, of which transmembranous transport could be involved in volume regulation [2,28].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Isotonic Activation of Cell Volume Regulation in Rat Peritoneal Mesothelial Cells and in Kidney Outer Medullary Collecting Duct Principal Cells

et al. 2021

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“…entities, referred to as osmolytes. Increasing the values of the T m (melting temperature) and C m (melting concentration) of proteins, the correction of folding defects via reduction in the aggregation of proteins is the major attribute of osmolytes [ 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 ]. The osmoregulatory property of taurine corresponds to its presence at higher concentrations in cells exposed to higher levels of oxidants [ 187 , 188 , 189 ].…”

Section: Neuroprotective Effects Of Taurinementioning

confidence: 99%

Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases

et al. 2020

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Neurodegenerative diseases (NDs) are characterized by the accumulation of misfolded proteins. The hallmarks of protein aggregation in NDs proceed with impairment in the mitochondrial function, besides causing an enhancement in endoplasmic reticulum (ER) stress, neuroinflammation and synaptic loss. As accumulation of misfolded proteins hampers normal neuronal functions, it triggers ER stress, which leads to the activation of downstream effectors formulating events along the signaling cascade—referred to as unfolded protein response (UPRER) —thereby controlling cellular gene expression. The absence of disease-modifying therapeutic targets in different NDs, and the exponential increase in the number of cases, makes it critical to explore new approaches to treating these devastating diseases. In one such approach, osmolytes (low molecular weight substances), such as taurine have been found to promote protein folding under stress conditions, thereby averting aggregation of the misfolded proteins. Maintaining the structural integrity of the protein, taurine-mediated resumption of protein folding prompts a shift in folding homeostasis more towards functionality than towards aggregation and degradation. Together, taurine enacts protection in NDs by causing misfolded proteins to refold, so as to regain their stability and functionality. The present study provides recent and useful insights into understanding the progression of NDs, besides summarizing the genetics of NDs in correlation with mitochondrial dysfunction, ER stress, neuroinflammation and synaptic loss. It also highlights the structural and functional aspects of taurine in imparting protection against the aggregation/misfolding of proteins, thereby shifting the focus more towards the development of effective therapeutic modules that could avert the development of NDs.

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Osmolytes Offset the Urea’s Effect on Protein Structure and Function

Cited by 2 publications

References 120 publications

Comparison of Isotonic Activation of Cell Volume Regulation in Rat Peritoneal Mesothelial Cells and in Kidney Outer Medullary Collecting Duct Principal Cells

Comparison of Isotonic Activation of Cell Volume Regulation in Rat Peritoneal Mesothelial Cells and in Kidney Outer Medullary Collecting Duct Principal Cells

Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases

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