Diabetic Modulation of the Temperature Kinetics Properties of Cytochrome Oxidase Activity in Rat Brain Mitochondria

Katyare, Surendra S.; Patel, Samir P.; Modi, Hiren R.

doi:10.1007/s11064-007-9447-1

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…Break-points in the Arrhenius plot, although often controversial, can be observed in several membrane-bound and soluble enzymes. [35][36][37] A possible explanation for such a break in the linear Arrhenius plot is the presence of two conformational states that are both catalytically competent. [38,39] Other possible explanations for the non-linearity of these plots are thermal inactivation or a pH change in the A C H T U N G T R E N N U N G reaction buffer upon temperature.…”

Section: Effect Of Variants On E Amentioning

confidence: 99%

Fine‐Tuning of Catalytic Properties of Catechol 1,2‐Dioxygenase by Active Site Tailoring

Caglio

Valetti

Caposio³

et al. 2009

ChemBioChem

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Catechol 1,2-dioxygenases and chlorocatechol dioxygenases are Fe(III)-dependent enzymes that do not require a reductant to perform the ortho cleavage of the aromatic ring. The reaction mechanism is common to the two enzymes, and active-site residues must play a key role in the fine-tuning of specificity. Protein engineering was applied for the first time to the catalytic pocket of a catechol 1,2-dioxygenase by site-specific and site-saturation mutagenesis with the purpose of redesigning the pocket shape for improved catalysis on bulky derivatives. Mutants were analysed for changes in kinetic parameters: variants for residue 69 show an inversion of specificity with a preference towards 4-chlorocatechol (decrease of K(M) by a factor of 20) and activity on the rarely recognised substrate 4,5-dichlorocatechol, thus creating a novel, engineered chlorocatechol dioxygenase. A L69A substitution conveys gain-of-function activity towards 4-tert-butylcatechol. Mutations of position 72 enhance k(cat) towards chlorinated substrates. The biphasic Arrhenius plot observed in A72S suggests the involvement of a dynamic switch in the fine regulation of the enzyme.

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Section: Effect Of Variants On E Amentioning

confidence: 99%

Fine‐Tuning of Catalytic Properties of Catechol 1,2‐Dioxygenase by Active Site Tailoring

Caglio

Valetti

Caposio³

et al. 2009

ChemBioChem

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“…DM is divided according to the action of beta cells: Type I DM is characterized into the degeneration of beta cells, while the main cause of type II DM is a progressive decline in insulin sensitivity with eventual insulin deficiency that results in sustained hyperglycemia [1][2][3]. The latter is most common in humans and has a proportion of more than 97% in diabetic patients [4].…”

Section: Introductionmentioning

confidence: 99%

Effects of Treadmill Exercise on Cell Proliferation and Differentiation in the Subgranular Zone of the Dentate Gyrus in a Rat Model of Type II Diabetes

Hwang

Yoo

et al. 2008

Neurochem Res

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In the present study, we investigated the effects of a treadmill exercise on serum glucose levels and Ki67 and doublecortin (DCX) immunoreactivity, which is a marker of cell proliferation expressed during cell cycles except G0 and early G1 and a marker of progenitors differentiating into neurons, respectively, in the subgranular zone of the dentate gyrus (SZDG) using a type II diabetic model. At 6 weeks of age, Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats were put on a treadmill with or without running for 1 h/day/5 consecutive days at 22 m/min for 5 weeks. Body weight was significantly increased in the control (without running)-ZDF rats compared to that in the other groups. In the control groups blood glucose levels were increased by 392.7 mg/dl in the control-ZDF rats and by 143.3 mg/dl in the control-ZLC rats. However, in the exercise groups, blood glucose levels were similar between the exercise-ZLC and ZDF rats: The blood glucose levels were 110.0 and 118.2 mg/dl, respectively. Ki67 positive nuclei were detected in the SZDG in control and exercise groups. The number of Ki67 positive nuclei was significantly high in exercise groups compared to that in the control groups. In addition, Ki67 positive cells were abundant in ZLC groups compared to those in ZDF groups. DCX-immunoreactive structures in the control-ZDF rats were lower than that in the control-ZLC rats. In the exercise groups, DCX-immunoreactive structures (somata and processes with tertiary dendrites) and DCX protein levels were markedly increased in both the exercise-ZLC and ZDF rats compared to that in the control groups. These results suggest that a treadmill exercise reduces blood glucose levels in ZDF rats and increases cell proliferation and differentiation in the SZDG in ZLC and ZDF rats compared to those in control groups.

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Diabetes-induced abnormalities of mitochondrial function in rat brain cortex: the effect of n-3 fatty acid diet

2017

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Diabetic encephalopathy, a proven complication of diabetes is associated with gradually developing end-organ damage in the CNS increasing the risk of stroke, cognitive dysfunction or Alzheimer's disease. This study investigated the response of rat cortical mitochondria to streptozotocin-induced diabetes and the potential for fish oil emulsion (FOE) to modulate mitochondrial function. Diabetes-induced deregulation of the respiratory chain function as a result of diminished complex I activity (CI) and cytochrome c oxidase hyperactivity was associated with attenuation of antioxidant defense of isolated cortical mitochondria, monitored by SOD activity, the thiol content, the dityrosine and protein-lipid peroxidation adduct formation. A parallel reduction in phosphorylation of the energy marker AMPK has pointed out to disrupted energy homeostasis. Dietary FOE administration partially preserved CI activity, restored AMPK phosphorylation, but was unable to attenuate oxidative stress and prevent the shift toward saturated fatty acids in the cardiolipin composition. Moreover, diabetes has induced alterations in the protein expression of the regulatory COX4 subunit of cytochrome c oxidase, in the inhibitory factor IF1 and ATP5A subunit of FF-ATP synthase, in the uncoupling protein UCP4 and supramolecular organization of the respiratory complexes. FOE administration to diabetic rats has partially reversed these alterations. This study suggests diabetes-induced dysfunction of brain cortical mitochondria and its modulation by FOE administration. The intricate diabetic milieu and the n-3 FA nutrigenomic strength, however require further investigations to be able to unequivocally evaluate neuroprotective and adverse effects of FOE supplementation on the diabetic brain function.

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Diabetic Modulation of the Temperature Kinetics Properties of Cytochrome Oxidase Activity in Rat Brain Mitochondria

Cited by 3 publications

References 41 publications

Fine‐Tuning of Catalytic Properties of Catechol 1,2‐Dioxygenase by Active Site Tailoring

Fine‐Tuning of Catalytic Properties of Catechol 1,2‐Dioxygenase by Active Site Tailoring

Effects of Treadmill Exercise on Cell Proliferation and Differentiation in the Subgranular Zone of the Dentate Gyrus in a Rat Model of Type II Diabetes

Diabetes-induced abnormalities of mitochondrial function in rat brain cortex: the effect of n-3 fatty acid diet

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