Oxidative stress-mediated cytotoxicity of Endosulfan is causally linked to the inhibition of NADH dehydrogenase and Na+, K+-ATPase in Ehrlich ascites tumor cells

Murali, Megha; Carvalho, Mary Sweeta; Shivanandappa, T.

doi:10.1007/s11010-020-03711-z

Cited by 23 publications

(10 citation statements)

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“…Melatonin (Chakravarty & Rizvi, 2011), quercetin (Murali et al, 2020), PGE2 (Nepal et al, 2021) are examples of some other redox-active molecules (Radosinska & Vrbjar, 2021) These findings find parallels to the analysis of modulations of function in respiratory (Manoj & Bazhin, 2021), photosynthetic (Manoj et al, 2022e; and xenobiotic (Venkatachalam et al, 2016) metabolisms, which supports strongly for the ubiquitous relevance of murburn concept-based stochastic mechanism. Pubmed listed thousands of distinct reports for the specific search string "Na,K-ATPase and antioxidants" (since its discovery in 1957, until August 2022), signifying the premise that NKA function is actually redox-active.…”

Section: "Reversibility" Of Nka Reaction and The Action Of Ionophoresmentioning

confidence: 67%

“…This is when cysteine and GSH were found to ameliorate the inhibition of suckling rat brain NKA in galactosemia (Tsakiris et al, 2004). Melatonin (Chakravarty & Rizvi, 2011), quercetin (Murali et al, 2020), PGE2 (Nepal et al, 2021) are examples of some other redox‐active molecules (Radosinska & Vrbjar, 2021) that are known to affect NKA activity. Besides the above, diverse molecular topography and reactive moiety containing species like several oximes, propofol, phlorizin, acevaltrate, prilocaine, suloctidil, 4hydroxynonenal, ginsenoside, etc.…”

Section: Evidence That Nka Is a Murzymementioning

confidence: 99%

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Na,K‐ATPase: A murzyme facilitating thermodynamic equilibriums at the membrane‐interface

Manoj¹,

Gideon²,

Bazhin

et al. 2022

Journal Cellular Physiology

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The redox metabolic paradigm of murburn concept advocates that diffusible reactive species (DRS, particularly oxygen-centric radicals) are mainstays of physiology, and not mere pathological manifestations. The murburn purview of cellular function also integrates the essential principles of bioenergetics, thermogenesis, homeostasis, electrophysiology, and coherence. In this context, any enzyme that generates/ modulates/utilizes/sustains DRS functionality is called a murzyme. We have demonstrated that several water-soluble (peroxidases, lactate dehydrogenase, hemogoblin, etc.) and membrane-embedded (Complexes I-V in mitochondria, Photosystems I/II in chloroplasts, rhodopsin/transducin in rod cells, etc.) proteins serve as murzymes. The membrane protein of Na,K-ATPase (NKA, also known as sodium-potassium pump) is the focus of this article, owing to its centrality in neurocardio-musculo electrophysiology. Herein, via a series of critical queries starting from the geometric/spatio-temporal considerations of diffusion/mass transfer of solutes in cells to an update on structural/distributional features of NKA in diverse cellular systems, and from various mechanistic aspects of ion-transport (thermodynamics, osmoregulation, evolutionary dictates, etc.) to assays/explanations of inhibitory principles like cardiotonic steroids (CTS), we first highlight some unresolved problems in the field. Thereafter, we propose and apply a minimalist murburn model of trans-membrane ion-differentiation by NKA to address the physiological inhibitory effects of trans-dermal peptide, lithium ion, volatile anesthetics, confirmed interfacial DRS + proton modulators like nitrophenolics and unsaturated fatty acid, and the diverse classes of molecules like CTS, arginine, oximes, etc. These explanations find a pan-systemic connectivity with the inhibitions/uncouplings of other membrane proteins in cells.

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Section: "Reversibility" Of Nka Reaction and The Action Of Ionophoresmentioning

confidence: 67%

Section: Evidence That Nka Is a Murzymementioning

confidence: 99%

Na,K‐ATPase: A murzyme facilitating thermodynamic equilibriums at the membrane‐interface

Manoj¹,

Gideon²,

Bazhin

et al. 2022

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…This is when cysteine and GSH were found to ameliorate the inhibition of suckling rat brain NKA in galactosemia (Tsakiris et al, 2004). Melatonin (Chakravarty & Rizvi, 2011), quercetin (Murali et al, 2020), PGE2 (Nepal et al, 2021) are examples of some other redoxactive molecules (Radosinska & Vrbjar, 2021) that are known affect NKA activity. Besides the above, diverse molecular topography and reactive moiety containing species like several oximes, propofol, phlorizin, acevaltrate, prilocaine, suloctidil, 4hydroxynonenal, ginsenoide, etc.…”

Section: Reports Of Drs-involving and Phase-dependent Physiology Of Nkamentioning

confidence: 99%

Is the beta-subunit of Na,K-ATPase (NKA) a murzyme? Explaining the modulations by lithium ion, trans-dermal peptide, cardiotonic steroids, volatile anesthetics, arginine, dinitrophenol, and diverse antioxidants in NKA-aided neuro-musculo-electrophysiology

Manoj¹,

Nirusimhan²,

Gideon³

2022

Preprint

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The redox metabolic and bioenergetic paradigm of murburn concept advocates that diffusible reactive species (DRS, particularly oxygen-centric 1e-active radicals) are a crucial mainstay of physiology, and not mere pathological manifestations. The murburn purview of cellular function also integrates the essential principles of bioenergetics, thermogenesis, homeostasis, electrophysiology and coherence. In this context, any enzyme that generates/utilizes/sustains DRS functionality is called a murzyme. We have demonstrated that several water-soluble (hemoglobin, lactate dehydrogenase, peroxidases, etc.) and membrane-embedded (Complexes I-V in mitochondria, Photosystems I/II in chloroplasts, rhodopsin/transducin in rod cells, etc.) proteins serve as murzymes (Manoj & Gideon, BBA-Biomem., 2022). In the first part of our work on NKA (Na,K-ATPase), we had effectively questioned the classical mechanistic understanding of how this protein supposedly aids cells by stoichiometrically pumping 3 Na+ outward and 2 K+ inward per molecule of ATP, at ~ 102 cycles per second (Manoj et al., OSF Preprints 2022). In the second part, herein, we propose and apply a minimalist murburn model of trans-membrane ion differentiation by NKA to address the physiological inhibitory effects of trans-dermal peptide (thereby, clarifying upon the role of beta-subunit of NKA to recruit DRS), lithium ion, cardiotonic steroids, volatile anesthetics, confirmed interfacial DRS+proton modulators like nitrophenolics and oleate/oleic acid, diverse classes of molecules like the amino acid arginine, oximes, N-/O- heteroatom alkyl substituted molecules, etc. These explanations find a pan-systemic connectivity with the inhibitions/uncouplings of other membrane-proteins in cells. Further, we also moot new avenues to explore NKA structure-function correlations.

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“…Dehydrogenase is an enzyme that plays a role in the formation of ATP [56]. Inactivated dehydrogenase enzymes can produce a cytotoxic effect, resulting in a decrease in ATP where the cell's functional activity is affected, and the cell dies [57].…”

Section: Anticancermentioning

confidence: 99%

The Evolution of Pharmacological Activities Bouea macrophylla Griffith In Vivo and In Vitro Study: A Review

2022

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Bouea macrophylla Griffith (B. macrophylla) is one of the many herbal plants found in Asia, and its fruit is plum mango. This plant is rich in secondary metabolites, including flavonoids, tannins, polyphenolic compounds, and many others. Due to its bioactive components, plum mango has powerful antioxidants that have therapeutic benefits for many common ailments, including cardiovascular disease, diabetes, and cancer. This review describes the evolution of plum mango’s phytochemical properties and pharmacological activities including in vitro and in vivo studies. The pharmacological activities of B. macrophylla Griffith reviewed in this article are antioxidant, anticancer, antihyperglycemic, antimicrobial, and antiphotoaging. Each of these pharmacological activities described and studied the possible cellular and molecular mechanisms of action. Interestingly, plum mango seeds show good pharmacological activity where the seed is the part of the plant that is a waste product. This can be an advantage because of its economic value as a herbal medicine. Overall, the findings described in this review aim to allow this plant to be explored and utilized more widely, especially as a new drug discovery.

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Oxidative stress-mediated cytotoxicity of Endosulfan is causally linked to the inhibition of NADH dehydrogenase and Na+, K+-ATPase in Ehrlich ascites tumor cells

Cited by 23 publications

References 58 publications

Na,K‐ATPase: A murzyme facilitating thermodynamic equilibriums at the membrane‐interface

Na,K‐ATPase: A murzyme facilitating thermodynamic equilibriums at the membrane‐interface

Is the beta-subunit of Na,K-ATPase (NKA) a murzyme? Explaining the modulations by lithium ion, trans-dermal peptide, cardiotonic steroids, volatile anesthetics, arginine, dinitrophenol, and diverse antioxidants in NKA-aided neuro-musculo-electrophysiology

The Evolution of Pharmacological Activities Bouea macrophylla Griffith In Vivo and In Vitro Study: A Review

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