Disease relevance of Aco1

• Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion [1].
• When compared to controls, female offspring of our IUGR rat model exhibit higher expression (mRNA) of ANP and the atrial isoform of the myosin light chain, lower levels of Na+,K+-ATPase beta1 protein, increased cardiomyocyte depth and volume, increased sarcomere length, diminished cardiomyocyte contractility and lower aconitase activity [2].
• The results show that aconitase is not an enzyme particularly sensitive towards alloxan inhibition and thus apparently not a primary site for mediation of alloxan toxicity as it is the glucokinase [3].

High impact information on Aco1

• This is further demonstrated by IL-1 beta-induced inhibition of glucose oxidation by purified beta-cells, mitochondrial aconitase activity of dispersed islet cells, and mitochondrial aconitase activity of Rin-m5F cells, all of which are prevented by NMMA [4].
• Thus, the response of mitochondrial aconitase and ATP-dependent proteolytic activity to reperfusion-induced prooxidant production appears to be a regulated event that would be expected to reduce irreparable damage to the mitochondria [1].
• Aconitase was found to associate with the iron binding protein frataxin exclusively during reperfusion [1].
• Iron differentially stimulates translation of mitochondrial aconitase and ferritin mRNAs in mammalian cells. Implications for iron regulatory proteins as regulators of mitochondrial citrate utilization [5].
• These results suggest that zinc and iron interact negatively with cytosolic aconitase, but prove beneficial in reducing the oxidative stress, apart from improving functional integrity and iron/zinc status [6].

Biological context of Aco1

• By contrast, NMDA- or kainate (KA)-induced mitochondrial aconitase inactivation and cell death was inhibited by MnTBAP, but not MnTE-2-PyP [7].
• Mitochondrial aconitase inactivation and 8-hydroxy-2-deoxyguanosine (8-OHdG) were used as indices of steady-state mitochondrial superoxide (O(2)(-)) production and oxidative DNA damage, respectively [8].
• The activities of the enzymes common to both the Krebs cycle and the glyoxylate cycle (citrate synthase, aconitase, and malate dehydrogenase) were 20-40% higher in newborn than in adult rats [9].

Anatomical context of Aco1

• Left cardiac ventricles were removed and used for monitoring changes in several key genes, Na+,K+-ATPase beta1 protein expression, cardiomyocyte morphology and contractility as well as citrate synthase and aconitase activities [2].
• This is the first time that superoxide anions or NO has been shown to inactivate aconitase and oxoglutarate dehydrogenase in skeletal muscle [10].
• Again, dialuric acid and BuOOH were less potent inhibitors while ninhydrin and NEM were more potent inhibitors of aconitase in intact liver cells [3].
• Alloxan inhibited aconitase with a half maximal inhibitory concentration of 0.5 mM in sonically disrupted and 2.3 mM in intact isolated liver mitochondria [3].

Associations of Aco1 with chemical compounds

• Manganese exposure altered the dynamics of IRP-1 binding and the intracellular abundance of IRP-2, and altered the cellular abundance of transferrin receptor, ferritin, and mitochondrial aconitase protein levels [11].
• These data suggest that mitochondrial aconitase inactivation closely correlates with subsequent neuronal death following excitotoxicity produced by OGD or NMDA/KA exposure [7].
• Using the inactivation of mitochondrial and cytosolic aconitases as markers of compartment-specific superoxide (O2(-)) production, we show that oxygen-glucose deprivation (OGD) or excitotoxin exposure produce a time-dependent inactivation of mitochondrial, but not cytosolic, aconitase in cortical cultures [7].
• The maximal activities of aconitase and oxoglutarate dehydrogenase were both decreased by 25-30% by superoxide anions; however, only the maximal activity of aconitase was decreased, by approximately 50%, by incubation of muscles with SNP [10].
• NO is rapidly transformed to nitrite in aqueous solution, and NO activates heme-containing enzymes such as guanylyl cyclase and inhibits iron-sulfur enzymes such as mitochondrial aconitase [12].

Regulatory relationships of Aco1

• On the other hand, hemin partially counteracted the IL-1 beta induced decrease in aconitase activity, glucose oxidation, insulin release and medium insulin accumulation [13].

Other interactions of Aco1

• Modulation of aconitase, metallothionein, and oxidative stress in zinc-deficient rat intestine during zinc and iron repletion [6].
• The calculated distances of Acon-1 to c and Hbb are 30.1 +/- 5.0 and 36.1 +/- 5.3 cM, respectively [14].
• The genetic basis of these markers (Acon-1, Ahd-2, and Akp-1) was confirmed [15].
• To determine if mitochondrial O2(-) production was an important determinant in neuronal death resulting from OGD, metalloporphyrins with varying superoxide dismutase (SOD) activity were tested for their ability to protect against mitochondrial aconitase inactivation and cell death [7].
• OGD-induced mitochondrial aconitase inactivation and cell death was inhibited by manganese tetrakis (4-benzoic acid) porphyrin (MnTBAP), manganese tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) and NMDA receptor antagonists [7].

Analytical, diagnostic and therapeutic context of Aco1

• Aconitase activity exhibited a decline in activity followed by reactivation during cardiac reperfusion [1].

References