Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease

Maiese, Kenneth

doi:10.2174/1567202613666161129112822

Cited by 35 publications

(26 citation statements)

References 147 publications

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“…AMPK also can increase nicotinamide phosphoribosyltransferase (NAMPT) activity to convert nicotinamide to nicotinamide mononucleotide (31, 44, 45). This conversion of nicotinamide increases nicotinamide adenine dinucleotide (NAD + ) levels and decreases levels of the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae ) (SIRT1) inhibitor nicotinamide (39, 46, 47). …”

Section: Trpv1 Mtor Ampk and Aktmentioning

confidence: 99%

Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin

Maiese

2017

CNR

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BACKGROUND Transient receptor potential (TRP) channels are a superfamily of ion channels termed after the trp gene in Drosophila that are diverse in structure and control a wide range of biological functions including cell development and growth, thermal regulation, and vascular physiology. Of significant interest is the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, also known as the capsaicin receptor and the vanilloid receptor 1, that is a non-selective cation channel sensitive to a host of external stimuli including capsaicin and camphor, venoms, acid/basic pH changes, and temperature. METHODS Given the multiple modalities that TRPV1 receptors impact in the body, we examined and discussed the role of these receptors in vasomotor control, metabolic disorders, cellular injury, oxidative stress, apoptosis, autophagy, and neurodegenerative disorders and their overlap with other signal transduction pathways that impact trophic factors. RESULTS Surprisingly, TRPV1 receptors do not rely entirely upon calcium signaling to affect cellular biology, but also have a close relationship with the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and protein kinase B (Akt) that have roles in pain sensitivity, stem cell development, cellular survival, and cellular metabolism. These pathways with TRPV1 converge in the signaling of growth factors with recent work highlighting a relationship with erythropoietin (EPO). Angiogenesis and endothelial tube formation controlled by EPO requires, in part, the activation of TRPV1 receptors in conjunction with Akt and AMPK pathways. CONCLUSIONS TRPV1 receptors could prove to become vital to target disorders of vascular origin and neurodegeneration. Broader and currently unrealized implementations for both EPO and TRPV1 receptors can be envisioned for for the development of novel therapeutic strategies in multiple systems of the body.

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Section: Trpv1 Mtor Ampk and Aktmentioning

confidence: 99%

Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin

Maiese

2017

CNR

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“…MicroRNAs (miRNAs) are cluster of non-coding RNAs that trigger mRNA degradation and repress translation function mainly by targeting messenger RNAs (mRNAs) ( 109 ). Recently, the importance of miRNAs-mediated sirt1 regulation in diabetic vascular complications has gradually emerged ( 110 ). One extensively investigated miRNA was miR-34a ( 111 , 112 ).…”

Section: Sirt1 Antagonizes Oxidative Stress In Diabetic Mellitusmentioning

confidence: 99%

SIRT1 Antagonizes Oxidative Stress in Diabetic Vascular Complication

2020

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Diabetic mellitus (DM) is a significant public health concern worldwide with an increased incidence of morbidity and mortality, which is particularly due to the diabetic vascular complications. Several pivotal underlying mechanisms are associated with vascular complications, including hyperglycemia, mitochondrial dysfunction, inflammation, and most importantly, oxidative stress. Oxidative stress triggers defective angiogenesis, activates pro-inflammatory pathways and causes long-lasting epigenetic changes to facilitate the development of vascular complications. Therefore, therapeutic interventions targeting oxidative stress are promising to manage diabetic vascular complications. Sirtuin1 (SIRT1), a class III histone deacetylase belonging to the sirtuin family, plays critical roles in regulating metabolism and ageing-related pathological conditions, such as vascular diseases. Growing evidence has indicated that SIRT1 acts as a sensing regulator in response to oxidative stress and attenuates vascular dysfunction via cooperating with adenosine-monophosphate-activated protein kinase (AMPK) to activate antioxidant signals through various downstream effectors, including peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1α), forkhead transcription factors (FOXOs), and peroxisome proliferative-activated receptor α (PPARα). In addition, SIRT1 interacts with hydrogen sulfide (H2S), regulates NADPH oxidase, endothelial NO synthase, and mechanistic target of rapamycin (mTOR) to suppress oxidative stress. Furthermore, mRNA expression of sirt1 is affected by microRNAs in DM. In the current review, we summarize recent advances illustrating the importance of SIRT1 in antagonizing oxidative stress. We also discuss whether modulation of SIRT1 can serve as a therapeutic strategy to treat diabetic vascular complications.

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“…In regards to AMPK, AMPK blocks mTORC1 activity through the hamartin (tuberous sclerosis 1)/tuberin (tuberous sclerosis 2) (TSC1/TSC2) complex that inhibits mTORC1 (246,247) (Figure 3). Control of the TSC1/TSC2 complex also is controlled though phosphoinositide 3-kinase (PI 3-K), Akt, and its phosphorylation of TSC2.…”

Section: Mtor and Amp Activated Protein Kinasementioning

confidence: 99%

New Insights for nicotinamide Metabolic disease autophagy and mTOR

Maiese

2020

Front Biosci

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Metabolic disorders, such as diabetes mellitus (DM), are increasingly becoming significant risk factors for the health of the global population and consume substantial portions of the gross domestic product of all nations. Although conventional therapies that include early diagnosis, nutritional modification of diet, and pharmacological treatments may limit disease progression, tight serum glucose control cannot prevent the onset of future disease complications. With these concerns, novel strategies for the treatment of metabolic disorders that involve the vitamin nicotinamide, the mechanistic target of rapamycin (mTOR), mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), AMP activated protein kinase (AMPK), and the cellular pathways of autophagy and apoptosis offer exceptional promise to provide new avenues of treatment. Oversight of these pathways can promote cellular energy homeostasis, maintain mitochondrial function, improve glucose utilization, and preserve pancreatic β-cell function. Yet, the interplay among mTOR, AMPK, and autophagy pathways can be complex and affect desired clinical outcomes, necessitating further investigations to provide efficacious treatment strategies for metabolic dysfunction and DM.

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Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease

Cited by 35 publications

References 147 publications

Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin

Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin

SIRT1 Antagonizes Oxidative Stress in Diabetic Vascular Complication

New Insights for nicotinamide Metabolic disease autophagy and mTOR

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