Drug-induced protein changes

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

Beere, H.M., Morimoto, R.I., Hickman, J.A. (1993). Investigations of mechanisms of drug-induced changes in gene expression N methylformamide-induced changes in synthesis of the M(r) 72,000 constitutive heat shock protein during commitment of HL-60 cells to granulocyte differentiation. Cancer Res. 53, 3034—3039. 

The arrangement of the proteins within the membrane seems to depend to some extent on the electrostatic surface potential and interface permittivity. It is influenced by electrostatic interaction between the proteins, polar head groups of the phospholipid and ions within the aqueous medium of the membrane surface. This can be affected by exogenous molecules such as drugs. Phospholipid-induced conformational change in intestinal calcium-binding protein in the absence and presence of Ca2+ has been described [37]. There is, however, no doubt that hydrophobic interactions between peptides and membrane interfaces play an important role. A general frame-... 

There are numerous methods to determine the nephrotoxic potential of a chemical or to study the mechanism(s) by which a chemical induces nephrotoxicity. In humans, the concern is most often related to either drug-induced or occupationally associated nephrotoxicity. Evaluation of nephrotoxicity in humans is limited primarily to the measurement of urinary changes (e.g., volume, enzymes, protein, etc.), BUN or serum creatinine concentrations, creatinine clearance, or renal biopsy. The measurement of an increase in urinary N-acetyl-jS-D-glucosaminidase (NAG) or alanine aminopeptidase (AAP) levels,... 

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