Rustenbeck 1998 Biochem Pharmacol
| Rustenbeck I, Eggers G, Reiter H, Münster W, Lenzen S (2020) Polyamine modulation of mitochondrial calcium transport. I. Stimulatory and inhibitory effects of aliphatic polyamines, aminoglucosides and other polyamine analogues on mitochondrial calcium uptake. Biochem Pharmacol 56:977–85. |
Rustenbeck I, Eggers G, Reiter H, Münster W, Lenzen S (2020) Biochem Pharmacol
Abstract: In this study, the regulation of mitochondrial Ca2+ transport by polyamines structurally related to spermine and by analogous polycationic compounds was characterized. Similar to spermine, a number of amino groups containing cationic compounds exerted a dual effect on Ca2+ transport of isolated rat liver mitochondria: a decrease in Ca2+ uptake velocity and an enhancement of Ca2+ accumulation. In contrast to the effects of spermine and other aliphatic polyamines, however, the accumulation-enhancing effect of aminoglucosides, basic polypeptides, and metal-amine complexes turned into an inhibition of Ca2+ accumulation at higher concentrations. Within groups of structurally related compounds, the potency to decrease Ca2+ uptake velocity and to enhance Ca2+ accumulation correlated with the number of cationic charges. The presence of multiple, distributed cationic charges was a necessary, but not sufficient criterion for effects on mitochondrial Ca2+ transport, because cationic polyamines and basic oligopeptides which did not enhance mitochondrial Ca2+ accumulation could be identified. Spermine was not able to antagonize the blocking of Ca2+ uptake by ruthenium red, but rather showed an apparent synergism, which can be explained as a displacement of membrane-bound Ca2+ by spermine. The aminoglucosides, gentamicin and neomycin, but not the inactive polyamine bis(hexamethylene)-triamine, inhibited the binding of spermine to intact mitochondria. Apparently, the binding of spermine, gentamicin, and a number of polyamine analogues to low-affinity binding sites at mitochondria, which have low, but distinct structural requirements and which may correspond to phospholipid headgroups, indirectly influences the activity state of the mitochondrial Ca2+ uniporter. The ability of aminoglucosides to displace spermine from the mitochondria and to inhibit mitochondrial Ca2+ accumulation may contribute to the mitochondrial lesions, which are known to occur early in the course of aminoglucoside-induced nephrotoxicity.
Labels: MiParea: Pharmacology;toxicology
Organism: Rat
Tissue;cell: Liver
Preparation: Isolated mitochondria
Regulation: Calcium, Ion;substrate transport
Spermidine
