Insulin injections inhibits PTZ-induced mitochondrial dysfunction, oxidative stress and neurological deficits via the SIRT1/PGC-1α/SIRT3 pathway

Cheng, Yanxiang; Zeng, Xin; Mai, Qianting; Bai, Xinying; Jiang, Yuan; Li, Jinjin; Fan, Shiqi; Ding, Hong

doi:10.1016/j.bbadis.2021.166124

Cited by 11 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

mentioning

confidence: 99%

“…17 SIRT1 influences the activity of mitochondria by reducing the levels of mitochondrial reactive oxygen species (mtROS), 18 potentially preserving their oxidative phosphorylation efficiency and dynamics. [19][20][21] In humans, some indirect observation with resveratrol (a SIRT1 activator) 22 shows encouraging findings, and some trials involving SIRT1 agonists are currently ongoing. 9 However, evidence is limited and, in part, controversial.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels

Mengozzi

Costantino

Paneni

et al. 2022

Circulation Research

View full text Add to dashboard Cite

BACKGROUND: Experimental evidence suggests a key role of SIRT1 (silent information regulator 1) in age- and metabolic-related vascular dysfunction. Whether these effects hold true in the human microvasculature is unknown. We aimed to investigate the SIRT1 role in very early stages of age- and obesity-related microvascular dysfunction in humans. METHODS: Ninety-five subjects undergoing elective laparoscopic surgery were recruited and stratified based on their body mass index status (above or below 30 kg/m 2 ) and age (above or below 40 years) and in 4 groups: Young Nonobese, Young Obese, Old Nonobese, and Old Obese. we measured small resistance arteries’ endothelial function by pressurized micromyography before and after incubation with a SIRT1 agonist (SRT1720) and a mitochondria reactive oxygen species scavenger (MitoTEMPO). We assessed vascular levels of mitochondria ROS and nitric oxide availability by confocal microscopy and vascular gene expression of SIRT1 and mitochondrial proteins by qPCR. Chromatin immunoprecipitation assay was employed to investigate SIRT1-dependent epigenetic regulation of mitochondrial proteins. RESULTS: Compared with Young Nonobese, obese and older patients showed lower vascular expression of SIRT1 and antioxidant proteins (FOXO3 [forkhead box protein O3] and SOD2) and higher expression of pro-oxidant and aging mitochondria proteins p66 Shc and Arginase II. Old Obese, Young Obese and Old Nonobese groups endothelial dysfunction was rescued by SRT1720. The restoration was comparable to the one obtained with mitoTEMPO. These effects were explained by SIRT1-dependent chromatin changes leading to reduced p66 Shc expression and upregulation of proteins involved in mitochondria respiratory chain. CONCLUSIONS: SIRT1 is a novel central modulator of the earliest microvascular damage induced by age and obesity. Through a complex epigenetic control mainly involving p66 Shc and Arginase II, it influences mitochondria ROS levels, NO availability, and the expression of proteins of the mitochondria respiratory chain. Therapeutic modulation of SIRT1 restores obesity- and age-related endothelial dysfunction. Early targeting of SIRT1 might represent a crucial strategy to prevent age- and obesity-related microvascular dysfunction.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels

Mengozzi

Costantino

Paneni

et al. 2022

Circulation Research

View full text Add to dashboard Cite

show abstract

“…Administration of insulin has been proven to increase neuroprotective mechanisms and decrease seizure frequency. [13] The occurrence of epilepsy in the pediatric diabetic population of the diabetes clinic at the Royal Children's Hospital, Melbourne, Australia, was 0.9% [3] There is a rise in antioxidant enzymes such as SOD, GSH-Px, and CAT present in the brain. There has been an observed decrease in enzyme activity of the electron transport chain (ETC) in hippocampi, and increased oxidative stress has been seen in a rat model.…”

Section: Insulinmentioning

confidence: 99%

Genethormonal Outlook of Epilepsy: A Case Report Associated with Catamenial Epilepsy

Mehta,

Patel,

Shah

2023

Int J Res Rev

View full text Add to dashboard Cite

Epilepsy can be considered as unprovoked seizures within 24 hours. From decades, seizures shrouded even when CNS was not studied. With the help of case study, we have tried to point out a hypothetical point correlating genetically acquired epilepsy and catamenial epilepsy. So far, studies have been conducted on the influence of female sex hormones upon differently oriented electrical charges in the brain and related complications. The present article describes genetic variations and hormonal changes as two sides of the disease condition. We have tried to explain the mechanism of QARS gene mutation from previously researched data and an evidence-based study of the same has been done for a better understanding of the reader. The article has aimed discussion upon etiological factors including female sex hormones, thyroid hormones, insulin, prolactin, alteration in bone metabolism, adrenal hormones, and genetic epilepsy for better apprehension of pathological conditions. Keywords: Catamenial epilepsy, genetic epilepsy, adrenal hormones, unprovoked seizures

show abstract

“…As we have discussed in 1.1, SIRT1 has been proved to be downstream of SIRT1, thus SIRT1/PGC-1alpha/SIRT3 pathway might play an essential role in mitochondrial dysfunction, oxidative stress and related neurological deficits. ( Cheng et al, 2021 ).…”

Section: Sirt2 In Central Nervous System Cellsmentioning

confidence: 99%

“…Research on cardiomyopathy revealed that PGC-1α plays a role in moderating SIRT3, which in turn deacetylates enzymes to control antioxidants and the metabolization of mitochondrial energy (Zhu et al, 2020). Similarly, PGC-1α/SIRT3 pathway have been reported neuroprotective in hippocampus by preventing damage to mitochondria and preventing cell apoptosis and neuron loss (Cheng et al, 2021). As we have discussed in 1.1, SIRT1 has been proved to be downstream of SIRT1, thus SIRT1/ PGC-1alpha/SIRT3 pathway might play an essential role in mitochondrial dysfunction, oxidative stress and related neurological deficits.…”

Section: Sirt3 In Neurons In Central Nervous Systemmentioning

confidence: 99%

Sirtuins functions in central nervous system cells under neurological disorders

et al. 2022

View full text Add to dashboard Cite

The sirtuins (SIRTs), a class of NAD+ -dependent deacylases, contain seven SIRT family members in mammals, from SIRT1 to SIRT7. Extensive studies have revealed that SIRT proteins regulate virous cell functions. Central nervous system (CNS) decline resulted in progressive cognitive impairment, social and physical abilities dysfunction. Therefore, it is of vital importance to have a better understanding of potential target to promote homeostasis of CNS. SIRTs have merged as the underlying regulating factors of the process of neurological disorders. In this review, we profile multiple functions of SIRT proteins in different cells during brain function and under CNS injury.

show abstract

Insulin injections inhibits PTZ-induced mitochondrial dysfunction, oxidative stress and neurological deficits via the SIRT1/PGC-1α/SIRT3 pathway

Cited by 11 publications

References 46 publications

Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels

Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels

Genethormonal Outlook of Epilepsy: A Case Report Associated with Catamenial Epilepsy

Sirtuins functions in central nervous system cells under neurological disorders

Contact Info

Product

Resources

About