Melatonin attenuates diabetic cardiomyopathy and reduces myocardial vulnerability to ischemia‐reperfusion injury by improving mitochondrial quality control: Role of SIRT6

Journal of Pineal Research, Journal Year: 2020, Volume and Issue: 70(1)

Published: Oct. 5, 2020

Abstract Targeting mitochondrial quality control with melatonin has been found promising for attenuating diabetic cardiomyopathy (DCM), although the underlying mechanisms remain largely undefined. Activation of SIRT6 and membrane receptors exerts cardioprotective effects while little is known about their roles during DCM. Using high‐fat diet‐streptozotocin‐induced rat model, we that prolonged diabetes significantly decreased nocturnal circulatory heart levels, reduced expressions cardiac receptors, myocardial AMPK‐PGC‐1α‐AKT signaling. 16 weeks treatment inhibited progression DCM following ischemia‐reperfusion (MI/R) injury by reducing fission, enhancing biogenesis mitophagy via re‐activating After induction diabetes, adeno‐associated virus carrying SIRT6‐specific small hairpin RNA or luzindole was delivered to animals. We showed knockdown antagonizing abolished protective against dysfunction as evidenced aggravated fission mitophagy. Additionally, shRNA melatonin‐induced activation well its actions. Collectively, demonstrated long‐term attenuated vulnerability MI/R through preserving control. Melatonin receptor‐mediated SIRT6‐AMPK‐PGC‐1α‐AKT axis played a key role in this process. may be strategy patients.

Language: Английский

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Structural basis of ligand recognition at the human MT1 melatonin receptor

Nature, Journal Year: 2019, Volume and Issue: 569(7755), P. 284 - 288

Published: April 24, 2019

Language: Английский

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Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules, Journal Year: 2021, Volume and Issue: 26(9), P. 2506 - 2506

Published: April 25, 2021

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro vivo. Results showed the involvement anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction tumor growth metastases, side effects associated chemotherapy radiotherapy, decreasing drug resistance therapy, augmentation therapeutic conventional therapies. Clinical trials revealed an effective adjuvant to all This review summarized biosynthesis, availability from natural sources, metabolism, bioavailability, melatonin, its use clinical trials, pharmaceutical formulation. Studies discussed this will provide solid foundation for researchers physicians design develop new therapies treat prevent using melatonin.

Language: Английский

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Obesity and chronic kidney disease

AJP Endocrinology and Metabolism, Journal Year: 2022, Volume and Issue: 324(1), P. E24 - E41

Published: Nov. 16, 2022

The prevalence of obesity has increased dramatically during the past decades, which been a major health problem. Since 1975, number people with worldwide nearly tripled. An increasing studies find as driver chronic kidney disease (CKD) progression, and mechanisms are complex include hemodynamic changes, inflammation, oxidative stress, activation renin-angiotensin-aldosterone system (RAAS). Obesity-related is characterized by glomerulomegaly, often accompanied localized segmental glomerulosclerosis lesions. In these patients, early symptoms atypical, microproteinuria being main clinical manifestation nephrotic syndrome rare. Weight loss RAAS blockers have protective effect on obesity-related CKD, but even so, significant proportion patients eventually progress to end-stage renal despite treatment. Thus, it critical comprehend underlying CKD create new tactics for slowing or stopping progression. this review, we summarize current knowledge disease, its pathological future perspectives

Language: Английский

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Phytomelatonin: An Emerging Regulator of Plant Biotic Stress Resistance

Trends in Plant Science, Journal Year: 2020, Volume and Issue: 26(1), P. 70 - 82

Published: Sept. 4, 2020

Language: Английский

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Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(6), P. 2437 - 2458

Published: Feb. 8, 2023

Language: Английский

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Protective Role of Melatonin and Its Metabolites in Skin Aging

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1238 - 1238

Published: Jan. 22, 2022

The skin, being the largest organ in human body, is exposed to environment and suffers from both intrinsic extrinsic aging factors. skin process characterized by several clinical features such as wrinkling, loss of elasticity, rough-textured appearance. This complex accompanied with phenotypic functional changes cutaneous immune cells, well structural disturbances extracellular matrix components collagens elastin. Because health considered one principal factors representing overall “well-being” perception “health” humans, anti-aging strategies have recently been developed. Thus, while fundamental mechanisms regarding are known, new substances should be for introduction into dermatological treatments. Herein, we describe melatonin its metabolites potential “aging neutralizers”. Melatonin, an evolutionarily ancient derivative serotonin hormonal properties, main neuroendocrine secretory product pineal gland. It regulates circadian rhythmicity also exerts anti-oxidative, anti-inflammatory, immunomodulatory, anti-tumor capacities. intention this review summarize within aging, research advances on molecular leading these changes, impact melatoninergic anti-oxidative system controlled metabolites, targeting prevention or reversal aging.

Language: Английский

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The Role of Tryptophan Metabolites in Neuropsychiatric Disorders

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 9968 - 9968

Published: Sept. 1, 2022

In recent decades, neuropsychiatric disorders such as major depressive disorder, schizophrenia, bipolar, etc., have become a global health concern, causing various detrimental influences on patients. Tryptophan is an important amino acid that plays indisputable role in several physiological processes, including neuronal function and immunity. Tryptophan’s metabolism process the human body occurs using different pathways, kynurenine serotonin pathways. Furthermore, other biologically active components, serotonin, melatonin, niacin, are by-products of Current evidence suggests functional imbalance synthesis metabolites causes appearance pathophysiologic mechanisms leads to diseases. This review summarizes pharmacological tryptophan its development disorders. addition, quantification following neurotransmitters precursor highlighted. Eventually, efficiency biomarkers inflammatory, protein, electrophysiological, genetic, proteomic diagnosis/treatment was discussed understand biomarker application detection/treatment

Language: Английский

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Evidence for the Benefits of Melatonin in Cardiovascular Disease

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: June 20, 2022

The pineal gland is a neuroendocrine which produces melatonin, hormone with critical physiological roles in the circadian rhythm and sleep-wake cycle. Melatonin has been shown to possess anti-oxidant activity neuroprotective properties. Numerous studies have that melatonin significant functions cardiovascular disease, may anti-aging ability of decrease primary hypertension needs be more extensively evaluated. benefits reducing cardiac pathology, preventing death muscle response ischemia-reperfusion rodent species. Moreover, also prevent hypertrophy heart under some circumstances, turn would lessen development failure. Several currently used conventional drugs show cardiotoxicity as an adverse effect. Recent acts effective suppressing damage mediated by pharmacologic drugs. Therefore, cardioprotective multiple animal human studies. Herein, we summarize most established system focus on molecular mechanisms action.

Language: Английский

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Dual sources of melatonin and evidence for different primary functions

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: May 14, 2024

This article discusses data showing that mammals, including humans, have two sources of melatonin exhibit different functions. The best-known source melatonin, herein referred to as Source #1, is the pineal gland. In this organ, production circadian with maximal synthesis and release into blood cerebrospinal fluid occurring during night. Of total amount produced in we speculate less than 5% synthesized by rhythm has primary function influencing clock at level suprachiasmatic nucleus (the CSF melatonin) clockwork all peripheral organs via receptor-mediated actions. A second (Source # 2) from multiple tissues throughout body, probably being mitochondria these cells. constitutes bulk mammals concerned metabolic regulation. review emphasizes action determining re-dox homeostasis, but it other critical effects well. Extrapineal does not a released acts locally its cell origin possibly paracrine matter on adjacent factors control/influence extrapineal sites are unknown. We propose concentration cells determined subcellular redox state may be inducible under stressful conditions plant

Language: Английский

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