EFFECTS OF ADRIAMYCIN ON THE BALANCE OF GLOMERULAR PROTEIN-METABOLISM- STUDIES IN ISOLATED GLOMERULI OF THE ATLANTIC HAGFISH, MYXINE GLUTINOSA

Alterations in the glomerular metabolic balance such as an increase pr otein synthesis and/or diminished proteolytic activities with a concom itant enrichment of protein into the glomerulus have previously been a ssociated with various renal diseases. The present study was aimed to closer define which pathomechanisms initially cause alterations in glo merular protein metabolism by using the anthracycline antibiotic Adria mycin (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 appl ied. ADR pretreatment caused a significant increase in glomerular prot ein synthesis (control (c): 55.1 +/- 4.7 DPM/h/mu g protein, ADR: 90.7 +/- 7.5) accompanied by an elevated glomerular protein content. The s ulfhydryl donor N-acetylcysteine (NAG) was applied as a free radical s cavenger and showed no protective properties on the increase in protei n synthesis (ADR + NAG: 86.2 +/- 11.5 DPM/h/mu g protein). Further, AD R caused a significant inhibition of RNA synthesis (c: 12.3 +/- 1.2 DP M/h/mu g protein, ADR: 6.0 +/- 0.7). The proteolytic activity was dimi nished 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 rad ical-mediated effect of ADR on protein synthesis could possibly be rul ed out. It is suggested instead that the increased protein synthesis i s due to a net-effect of protein synthesis and proteolytic degradation occurring at the same time. The low translation rate caused by the la ck of RNA could be disguised by the diminished degradation of proteins . This leads over time to a net increase of protein synthesis and to a n enrichment of total protein in the glomerulus, subsequently causing functional alterations of the glomerular filtration barrier. A decreas ed glomerular proteolytic activity is therefore regarded to be the mos t crucial pathomechanism responsible for disturbances in the glomerula r protein balance during the development of ADR glomerulopathy in M, g lutinosa.