Mechanical membrane damage

Clofibrate causes a necrotizing myopathy, particularly in patients with renal failure, nephrotic syndrome or hypothyroidism. The myopathy is painful and myokymia of unknown origin is sometimes present. The mechanism of damage is not known, but p-chlorophenol is a major metabolite of clofibrate and p-chlorophe-nol is a particularly potent uncoupler of cellular oxidative phosphorylation and disrupts the fluidity of lipid membranes. Muscle damage is repaired rapidly on the cessation of treatment. 

Wolfe, J. and Bryant, G. 1992. Physical principles of membrane damage due to dehydration and freezing. In Mechanics of Swelling (T.K. Karalis, ed.), NATO ASI Series H64, pp. 205-224. Springer - Verlag, Berlin. 

Ultrastructural examination of duckweed frond (Fig. 5) and root tissues treated with 18 (100 xM) revealed membrane damage to the tonoplast after 12 hours of exposure. The samples viewed through the transmission electron microscope showed ruptured tonoplasts, free-floating organelles and loss of cytoplasm relative to control tissues. The tonoplast may be the primary target for the phytotoxic effect of 18, which represents an unusual, if not unique, toxic mechanism among phytotoxic agents. 

This dependence on light levels and temperature is believed to be due to the mechanism of production of isoprene in the plant, which involves the enzyme isoprene synthetase and dimethylallyl diphosphate (DMAPP) as a precursor to isoprene (e.g., see Silver and Fall, 1995 and Monson et al., 1995). Either the enzyme, the formation of DMAPP, or both may be light sensitive (Wildermuth and Fall, 1996). The temperature effect has been attributed to effects on the enzyme, increasing its activity initially and then leading to irreversible denaturation (and/or possibly membrane damage) (Fall and Wildermuth, 1998). 

Changes in membrane permeability might be expected to lead to osmolar imbalance and fetal abnormality. This is hypothetical, as there are no real examples of such a mechanism, although high doses of vitamin A are teratogenic and may cause ultras true tural membrane damage. 

Young J, Peterson C, Venge P, Cohn Z. 1986. Mechanism of membrane damage mediated by human eosinophil cationic protein. Nature. 321 613-616. 

It is postulated that inhibition of PtdCho synthesis and the release of choline are key steps associated with excitotoxicity and are common to NMDA and AMPA receptor stimulation. The mechanism of inhibition of PtdCho is not fully understood. Metabolic labeling experiments in cortical cultures demonstrate that NMDA receptor over activation does not modify the activity of phosphochohne or phospho-ethanolamine cytidylyltransferases but strongly inhibits choline and ethanolamine phosphotransferase activities. This effect is observed well before any significant membrane damage and cell death. Moreover, cholinephosphotransferase activity is lower in microsomes from NMDA-treated cells. These results show that membrane... 

Ibrahim, H.R., Sugimoto, Y., and Aoki, T. 2000. Ovotransferrin antimicrobial peptide (OTAP-92) kills bacteria through a membrane damage mechanism. Biochim. Biophys. Acta 1523, 196-205. 

Giuffrida S, De Guidi G, Miano P, Sortino S, Condorelli G, Costanzo LL. Molecular mechanism of drug photosensitization VIII effect of inorganic ions on membrane damage photosensitized by naproxen. / Inorg Biochem 1996 63 253-63. 

Figure 16.5. Mechanisms of membrane damage due to increased cytosolic calcium. [Adapted from Cotran, Kumar, and Collins (Eds.). Robbins Pathologic Basis of Disease, 6th ed., Elsevier Saunders, Philadelphia, 1999, Fig. 1-3, p. 6.]...

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