Alterations in the glomerular metabolic balance such as an increase protein synthesis and/or diminished proteolytic activities with a concomitant enrichment of protein into the glomerulus have previously been associated with various renal diseases. The present study was aimed to closer define which pathomechanisms initially cause alterations in glomerular protein metabolism by using the anthracycline antibiotic Adriamycin (ADR) as a model compound to experimentally induce a glomerular lesion. As an alternative multicellular system, isolated and in vitro-incubated glomeruli of the Atlantic hagfish Myxine glutinosa were applied. ADR pretreatment caused a significant increase in glomerular protein synthesis (control (c): 55.1 ± 4.7 DPM/h/µg protein, ADR: 90.7 ± 7.5) accompanied by an elevated glomerular protein content. The sulfhydryl donor N-acetylcysteine (NAC) was applied as a free radical scavenger and showed no protective properties on the increase in protein synthesis (ADR + NAC: 86.2 ± 11.5 DPM/h/µg protein). Further, ADR caused a significant inhibition of RNA synthesis (c: 12.3 ± 1.2 DPM/h/µg protein, ADR: 6.0 ± 0.7). The proteolytic activity was diminished in glomerular homogenates of ADR-treated animals (c: 4.91 ± 1.49 U/h/mg protein, ADR: 1.71 ± 1.02). Based on these results, a radical-mediated effect of ADR on protein synthesis could possibly be ruled out. It is suggested instead that the increased protein synthesis is due to a net-effect of protein synthesis and proteolytic degradation occurring at the same time. The low translation rate caused by the lack of RNA could be disguised by the diminished degradation of proteins. This leads over time to a net increase of protein synthesis and to an enrichment of total protein in the glomerulus, subsequently causing functional alterations of the glomerular filtration barrier. A decreased glomerular proteolytic activity is therefore regarded to be the most crucial patho-mechanism responsible for disturbances in the glomerular protein balance during the development of ADR glomerulopathy in M. glutinosa.

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