Improving Obesity and Insulin Resistance by Targeting Skeletal Muscle MKP-1

Bennett, Anton M.; Lawan, Ahmed

doi:10.33696/signaling.1.025

Cited by 2 publications

(1 citation statement)

References 67 publications

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“…One of the most important is H 2 O 2 -activated Ca/calmodulin-dependent kinase II (CAMKII) responsible for excitation–contraction coupling. In addition, JNKs (c-Jun N-terminal kinase) play an important role in insulin resistance, and p38 MAPK (p38 mitogen-activated protein kinase) has been shown to stimulate the uptake of glucose (Bennett and Lawan 2020 ). The activity of the protein kinase A (PKA) family depends on cellular levels of cyclic AMP (cAMP).…”

Section: Oxidative Stress Diseases Aging and Antioxidant Interventionsmentioning

confidence: 99%

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Jomova,

Raptova,

Alomar

et al. 2023

Arch Toxicol

363

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A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related factor 2 (Nrf2) and other processes. Increased levels of ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result in a harmful condition termed oxidative stress (“bad stress”). Although it is widely accepted, that many chronic diseases are multifactorial in origin, they share oxidative stress as a common denominator. Here we review the importance of oxidative stress and the mechanisms through which oxidative stress contributes to the pathological states of an organism. Attention is focused on the chemistry of ROS and RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl radicals, nitric oxide, peroxynitrite), and their role in oxidative damage of DNA, proteins, and membrane lipids. Quantitative and qualitative assessment of oxidative stress biomarkers is also discussed. Oxidative stress contributes to the pathology of cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s and Parkinson’s diseases, Down syndrome), psychiatric diseases (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, lung cancer), and aging. The concerted action of antioxidants to ameliorate the harmful effect of oxidative stress is achieved by antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), and small molecular weight antioxidants (vitamins C and E, flavonoids, carotenoids, melatonin, ergothioneine, and others). Perhaps one of the most effective low molecular weight antioxidants is vitamin E, the first line of defense against the peroxidation of lipids. A promising approach appears to be the use of certain antioxidants (e.g. flavonoids), showing weak prooxidant properties that may boost cellular antioxidant systems and thus act as preventive anticancer agents. Redox metal-based enzyme mimetic compounds as potential pharmaceutical interventions and sirtuins as promising therapeutic targets for age-related diseases and anti-aging strategies are discussed.

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Section: Oxidative Stress Diseases Aging and Antioxidant Interventionsmentioning

confidence: 99%

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Jomova,

Raptova,

Alomar

et al. 2023

Arch Toxicol

363

View full text Add to dashboard Cite

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Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?

Shillingford

Bennett

2023

Annu. Rev. Pharmacol. Toxicol.

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Phosphatases and kinases maintain an equilibrium of dephosphorylated and phosphorylated proteins, respectively, that are required for critical cellular functions. Imbalance in this equilibrium or irregularity in their function causes unfavorable cellular effects that have been implicated in the development of numerous diseases. Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of protein substrates on tyrosine residues, and their involvement in cell signaling and diseases such as cancer and inflammatory and metabolic diseases has made them attractive therapeutic targets. However, PTPs have proved challenging in therapeutics development, garnering them the unfavorable reputation of being undruggable. Nonetheless, great strides have been made toward the inhibition of PTPs over the past decade. Here, we discuss the advancement in small-molecule inhibition for the PTP subfamily known as the mitogen-activated protein kinase (MAPK) phosphatases (MKPs). We review strategies and inhibitor discovery tools that have proven successful for small-molecule inhibition of the MKPs and discuss what the future of MKP inhibition potentially might yield.

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Improving Obesity and Insulin Resistance by Targeting Skeletal Muscle MKP-1

Cited by 2 publications

References 67 publications

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?

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