Low molecular weight proteins

As stated earlier, proteins with a molecular weight lower than that of albumin are able to pass through the glomerular membrane in the kidney. Consequently, such low molecular weight proteins (LMWPs) are rapidly removed from the bloodstream. Following glomerular filtration, LMWPs are reabsorbed in the proximal tubular cells of the kidney. Since this process makes the kidney the major catabolic site for these proteins, they can be used as car- 

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Cadmium is effectively accumulated in the kidneys. When the cadmium concentration exceeds 200 gg/g in the kidney cortex, tubular damage will occur in 10% of the population, and proteins begin to leak into urine (proteinuria). When the concentration of cadmium in the kidney cortex exceeds 300 pg/g, the effect is seen in 50% of the exposed population. Typically, excretion of low-molecular weight proteins, such as beta-microglobulin, is increased, due to dysfunction of proximal tubular cells of the kidney. The existence of albumin or other high-molecular weight proteins in the urine indicates that a glomerular injury has also taken place. The excretion of protein-bound cadmium will also be increased. 

Carlsson, L., Nystrom, L.E., Sundkvist, 1.. Markey. F.. Lindberg, U. (1977). Actin polymerizability is influenced by profilin, a low molecular weight protein in non-muscle cells. J. Mol. Biol. 115, 465-483. 

Interferon is a low molecular weight protein, produced by vims-infected cells, that itself induces the formation of a second protein inhibiting the transcriphon of viral mRNA. Interferon is produced by the host cell in response to the vims particle, the viral nucleic and non-viral agents, including synthetic polynucleides such as polyinosinic acid polycytidylic acid (poly I C). There are two types of interferon. 

Bennett MS, Z Guan, M Laurberg, X-D Su (2001) Bacillus subtilis arsenate reductase is structurally and functionally similar to low molecular weight protein tyrosine phosphatases. Proc Natl Acad Sci USA 98 13577-13582. 

P2 Microglobulin A low-molecular-weight protein that may be elevated in multiple myeloma. 

McCarter, J.A., A.T. Mathieson, M. Roch, R.W. Olafson, and J.T. Buckley. 1982. Chronic exposure of coho salmon to sublethal concentrations of copper-II. Distribution of copper between high- and low-molecular weight proteins in liver cytosol and the possible role of metallothionein in detoxication. Comp. Biochem. Physiol. 72C 21-26. 

The urine frequently contains casts and amorphous debris, but rarely any considerable number of red blood corpuscles. Proteinuria and aminoaciduria are found in nearly all untreated patients from a very early age. The proteinuria is usually reported as albuminuria in the literature, but in some cases the urinary protein has been shown by electrophoresis to consist largely of a-globulin and other relatively low-molecular-weight proteins (B21). A similar urinary pattern occurs in a number of diseases of the renal tubule. The proteinuria is often only moderate in degree, e.g., < 50 to 150 mg protein per 100 ml of urine, but is easily detected by the conventional tests for protein, such as salicylsulfonic acid. Excretion of protein can rise to nearly 1 g/100 ml in some cases (H8, L7). 

Cojocel, C., Dociu, N., Maita, K., Sleight, S.D. and Hook, J.B. (1983). Effects of aminoglycosides on glomerular permeability, tubular reabsorption, and intracellular catabolism of the cationic low molecular weight protein lysozyme. Toxicol. Appl. Pharm. 39 129-139. 

C) cuboidal three-iron-four-sulfide [Fe3-S4] clusters—stable oxidation states are 0 and + 1 and (D) cubane four-iron-four-sulfide [Fe4-S4] clusters—stable oxidation states are + 1 and +2 for ferredoxin-type clusters and +2 and +3 for HIPIP clusters. Electrons can be delocalized, such that the valences of individual iron atoms lie between ferrous and ferric forms. Low-molecular-weight proteins containing the first and the last three types are referred to as rubredoxins (Rd) and ferredoxins (Fd), respectively. The protein ligands are frequently Cys residues, but a number of others are found, notably His, which replaces two of the thiol ligands in the [Fe2-S2] Rieske proteins. In addition to these, discrete Rd... 

Under semidry electrotransfer conditions, some low-molecular weight proteins are driven through the membranes, and because low buffer capacity limits run times, some high-molecular weight proteins are poorly transferred. 

Calmodulin This low-molecular-weight protein appears to depolymetize mkrotubules in the presence of calcium ion, but its exact role is unclear due to conflicting assertions about whether its action is directed toward tubulin and/or toward microtubule-associated proteins (Kakiuchi, 1982 Kumagai et aL, 1982 Lee and Wolff, 1982)... 

Renal Delivery Using Macromolecular Carriers The Low Molecular Weight Protein Approach 135... 

Low molecular weight proteins (LMWP) are freely filtered proteins with a molecular weight of less than 30 000 Dalton and are considered to be suitable as renal-specific drug carriers. The concept is based on four principles ... 

Figure 5.7. Schematic representation of the mechanism by which drug targeting to the proximal tubular cell of the kidney might be achieved using a low molecular weight protein (LMWP) as a carrier.

Figure 5.8. Renal specificity of a radiolabelled LMWP. Gamma-camera imaging after an intravenous injection of a radiolabelled low molecular weight protein (LMWP) in the rat, showing the predominant uptake of the LMWP by the kidneys.

In this chapter, macromolecular and pro-drug approaches for cell-selective therapeutic intervention in the proximal tubular cell have been described. Using a low-molecular weight protein as a drug carrier, the drug is delivered to the lysosomes of the proximal tubular cell... 

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