Effect of osmolytes on the fibrillation of HypF-N

Bhavsar, Rupen D.; Prasad, Shivcharan; Roy, Ipsita

doi:10.1016/j.biochi.2013.07.019

Cited by 6 publications

(7 citation statements)

References 18 publications

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“…To understand the mechanism of inhibition of insulin fibrillation by osmolytes, it is very important to identify the mode of interaction between insulin and the osmolytes at different stages of fibrillation of the protein. As mentioned earlier, although there is substantial literature with regard to protein stabilization by osmolytes 12 13 14 15 16 17 18 19 20 21 22 23 24 25 , there is very little data addressing the interaction behavior of inhibitors at different stages of protein fibrillation, especially focusing on the enthalpy of interaction 50 . In this work, isothermal titration calorimetry, an ultrasensitive technique for thermodynamic characterization of intermolecular interactions has been used to address the above issue.…”

Section: Resultsmentioning

confidence: 99%

“…Osmolytes are small organic molecules, several of which have been found to protect proteins from denaturation, misfolding, aggregation and amyloid formation under stressed environmental conditions 8 9 10 11 . Sugars, methylamines, polyols and some amino acids fall into this category and are found to reduce denaturation and aggregation of many proteins 12 13 14 15 16 17 18 19 . Osmolytes such as trehalose, ectoine and betaine have been found to protect enzyme functioning in extreme hot and cold environments 20 21 22 .…”

mentioning

confidence: 99%

“…There have been several reports in the literature on inhibition of fibrillation of proteins, in general 4 5 6 7 14 15 16 17 18 19 , and these include the use of different osmolytes 12 13 14 15 16 17 18 19 . Several disaccharides such as maltose, sucrose and trehalose have also been reported to increase the nucleation period of insulin fibrillation at a concentration of ~300 mM 45 .…”

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confidence: 99%

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Inhibition of insulin fibrillation by osmolytes: Mechanistic Insights

Choudhary

Kishore

Hosur

2015

Sci Rep

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We have studied here using a number of biophysical tools the effects of osmolytes, betaine, citrulline, proline and sorbitol which differ significantly in terms of their physical characteristics such as, charge distribution, polarity, H-bonding abilities etc, on the fibrillation of insulin. Among these, betaine, citrulline, and proline are very effective in decreasing the extent of fibrillation. Proline also causes a substantial delay in the onset of fibrillation in the concentration range (50–250 mM) whereas such an effect is seen for citrulline only at 250 mM, and in case of betaine this effect is not seen at all in the whole concentration range. The enthalpies of interaction at various stages of fibrillation process have suggested that the preferential exclusion of the osmolyte and its polar interaction with the protein are important in inhibition. The results indicate that the osmolytes are most effective when added prior to the elongation stage of fibrillation. These observations have significant biological implications, since insulin fibrillation is known to cause injection amyloidosis and our data may help in designing lead drug molecules and development of potential therapeutic strategies.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Inhibition of insulin fibrillation by osmolytes: Mechanistic Insights

Choudhary

Kishore

Hosur

2015

Sci Rep

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“…During the recent decades, it has been shown convincingly that osmoprotectors function by promoting protein refolding and suppressing aggregation of different proteins, both in vitro and in vivo [1,9,20,21,[62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. It should be noted that osmolytes may be capable of regulating the activity of the molecular chaperones GroEL, DnaK, and ClpB in a concentration-dependent manner [78][79][80].…”

Section: Protein Folding In Osmolyte Solutionsmentioning

confidence: 99%

Protein folding and stability in the presence of osmolytes

et al. 2016

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Osmolytes are molecules whose function, among others, is to balance the hydrostatic pressure between the intracellular and extracellular compartments. Accumulation of osmolytes in a cell occurs in response to stress caused by changes in pressure, temperature, pH, or the concentration of inorganic salts. Osmolytes can prevent the denaturation of native proteins and promote the renaturation of unfolded proteins. Investigation of the roles of osmolyte in these processes is essential for our understanding of the mechanisms of protein folding and function in vivo. The large number of published reports that have been devoted to the effects of osmolytes on proteins are not always consistent with each other. In this review, an attempt is made to systemize the array of data on this subject and to consider the problem of protein folding and stability in osmolyte solutions from a single viewpoint.

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“…Protein fibrillation is responsible for several amyloidogenic disorders including diseases such as Alzheimer's, Parkinson's, mad cow, diabetes type II, cystic fibroisis, and dialysis related amyloidosis [58,59]. Though there have been several studies describing the effects of osmolytes on fibrillation/aggregation of proteins [60][61][62][63][64][65][66], quantitative understanding in terms of energetics of interaction has only recently been addressed Page 3 of 5 [67,68]. Trehalose has been currently used for the treatment of Huntington's disease in transgenic animal mice [69].…”

Section: Role In Prevention Of Aggregation/fibrillation Of Proteinmentioning

confidence: 99%

Biological Wonders of Osmolytes: The Need to Know More

Judy¹,

Kishore²

2016

Biochem Anal Biochem

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Nature has selected osmolytes to protect intracellular macromolecules against denaturing stress conditions. These molecules are accumulated in the intracellular environment at considerably high concentrations. In general, osmolytes are known to stabilize proteins. However, under certain conditions, their destabilizing properties have also been pointed out. A careful qualitative and quantitative understanding of the mechanism of action of osmolytes with proteins from native to different stages of aggregation/fibrillation is extremely important in rational drug design. This review highlights the importance of naturally occurring osmolytes in protein folding, stabilization, and prevention of fibrillation/aggregation related diseases among others. Continued efforts are required to get quantitative insights into osmolyte-protein interactions along with experimental evidences for the much claimed preferential exclusion/preferential hydration phenomenon of osmolyte action. Mechanistic insights into the disease associated roles of osmolytes needs special attention.

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Effect of osmolytes on the fibrillation of HypF-N

Cited by 6 publications

References 18 publications

Inhibition of insulin fibrillation by osmolytes: Mechanistic Insights

Inhibition of insulin fibrillation by osmolytes: Mechanistic Insights

Protein folding and stability in the presence of osmolytes

Biological Wonders of Osmolytes: The Need to Know More

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