Dataset Information

Experimental and molecular docking studies of quercetin and vitamin E with diabetes-associated mitochondrial-ATPase as anti-apoptotic therapeutic strategies.

ABSTRACT:

Purpose

Researches have shown the relevance of antioxidants in the management of several diseases. In the present study, the effects of quercetin and vitamin E were investigated on the mitochondrial functions in vivo and in silico.

Methods

Structures of quercetin and vitamin E were docked against mitochondrial Adenosine triphosphatase (mATPase), and cytochrome c cavity. Activity of liver mATPase and mitochondrial permeability transition pore opening were determined by spectrophotometry and activation of cytochrome c was examined by immunohistochemistry.

Results

The binding energy of vitamin E (-9 Kcal/mol) in mATPase cavity compares well with glibenclamide (-9.4 Kcal/mol), while quercetin had a binding energy of -7.1 Kcal/mol. Similarly, vitamin E, quercetin were bound to cytochrome c by -6.4 and - 5.5 Kcal/mol energy, while glibenclamide had -7.0 Kcal/mol binding energy. The results showed that vitamin E was more accessible to the protoporphyrin prosthetic group in cytochrome c than quercetin. In the experimental studies, it was validated that vitamin E inhibited the uncontrolled activity of mATPase in diabetic rat liver. This was also proven and tested on the liver mitochondrial permeability transition pore opening observed in diabetic rats. Further experimental assessment of these on activation of cytochrome c showed that vitamin E reduced the extent of the activation more than quercetin and glibenclamide.

Conclusion

There is a favorable protein-ligand interaction between quercetin and vitamin E in certain apoptotic proteins implicated in diabetes complications.

SUBMITTER: Ojo OO

PROVIDER: S-EPMC9672242 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Experimental and molecular docking studies of quercetin and vitamin E with diabetes-associated mitochondrial-ATPase as anti-apoptotic therapeutic strategies.

Ojo Oluwatoyin O OO Ogunleke Titilayo T Ajeoge Joshua J Olorunsogo Olufunso O OO

Journal of diabetes and metabolic disorders 20220930 2

<h4>Purpose</h4>Researches have shown the relevance of antioxidants in the management of several diseases. In the present study, the effects of quercetin and vitamin E were investigated on the mitochondrial functions in vivo and in silico.<h4>Methods</h4>Structures of quercetin and vitamin E were docked against mitochondrial Adenosine triphosphatase (mATPase), and cytochrome c cavity. Activity of liver mATPase and mitochondrial permeability transition pore opening were determined by spectrophoto ...[more]

PMID: 36404854

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Project description:Leber hereditary optic neuropathy (LHON) and autosomal-dominant optic atrophy (DOA) are the two most common inherited optic neuropathies in the general population. Both disorders share striking pathological similarities, marked by the selective loss of retinal ganglion cells (RGCs) and the early involvement of the papillomacular bundle. Three mitochondrial DNA (mtDNA) point mutations; m.3460G>A, m.11778G>A, and m.14484T>C account for over 90% of LHON cases, and in DOA, the majority of affected families harbour mutations in the OPA1 gene, which codes for a mitochondrial inner membrane protein. Optic nerve degeneration in LHON and DOA is therefore due to disturbed mitochondrial function and a predominantly complex I respiratory chain defect has been identified using both in vitro and in vivo biochemical assays. However, the trigger for RGC loss is much more complex than a simple bioenergetic crisis and other important disease mechanisms have emerged relating to mitochondrial network dynamics, mtDNA maintenance, axonal transport, and the involvement of the cytoskeleton in maintaining a differential mitochondrial gradient at sites such as the lamina cribosa. The downstream consequences of these mitochondrial disturbances are likely to be influenced by the local cellular milieu. The vulnerability of RGCs in LHON and DOA could derive not only from tissue-specific, genetically-determined biological factors, but also from an increased susceptibility to exogenous influences such as light exposure, smoking, and pharmacological agents with putative mitochondrial toxic effects. Our concept of inherited mitochondrial optic neuropathies has evolved over the past decade, with the observation that patients with LHON and DOA can manifest a much broader phenotypic spectrum than pure optic nerve involvement. Interestingly, these phenotypes are sometimes clinically indistinguishable from other neurodegenerative disorders such as Charcot-Marie-Tooth disease, hereditary spastic paraplegia, and multiple sclerosis, where mitochondrial dysfunction is also thought to be an important pathophysiological player. A number of vertebrate and invertebrate disease models has recently been established to circumvent the lack of human tissues, and these have already provided considerable insight by allowing direct RGC experimentation. The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial optic neuropathies.

Dataset Information

Experimental and molecular docking studies of quercetin and vitamin E with diabetes-associated mitochondrial-ATPase as anti-apoptotic therapeutic strategies.

Purpose

Methods

Results

Conclusion

Publications

Experimental and molecular docking studies of quercetin and vitamin E with diabetes-associated mitochondrial-ATPase as anti-apoptotic therapeutic strategies.

Similar Datasets

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