Mitochondrial Sirtuins in Chronic Degenerative Diseases: New Metabolic Targets in Colorectal Cancer

Colloca, Antonino; Balestrieri, Anna; Anastasio, Camilla; Balestrieri, Maria Luisa

doi:10.3390/ijms23063212

Cited by 10 publications

(9 citation statements)

References 156 publications

(184 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among histone deacetylases, mitochondrial SIRT2, SIRT3, SIRT4, and SIRT5 are key metabolic enzymes controlling mitochondrial homeostasis and response to oxidative stress [ 3 , 27 , 28 , 29 ]. Compelling evidence indicates that mitochondrial sirtuins are involved in the regulation of endothelial function given their ability to regulate energy metabolism, ROS production, and cellular redox state [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondrial dysfunction occurring in the high-fat condition impairs endothelial homeostasis thus constituting a major risk factor for cardiovascular diseases, including diabetes, heart failure, pulmonary hypertension, and insulin resistance (IR) [ 1 ]. In this contest, mitochondrial sirtuins (SIRT) contribute to cellular homeostasis due to their pivotal roles in controlling metabolic processes as well as the responses to nutrient availability and oxidative stress [ 1 , 2 , 3 ]. SIRT, class III histone deacetylases, represent attractive tools for epigenetic intervention due to their crucial role in DNA damage repair and control of cell survival and metabolic homeostasis, including IR [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this contest, mitochondrial sirtuins (SIRT) contribute to cellular homeostasis due to their pivotal roles in controlling metabolic processes as well as the responses to nutrient availability and oxidative stress [ 1 , 2 , 3 ]. SIRT, class III histone deacetylases, represent attractive tools for epigenetic intervention due to their crucial role in DNA damage repair and control of cell survival and metabolic homeostasis, including IR [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

et al. 2022

Self Cite

View full text Add to dashboard Cite

Emerging evidence indicates that defects in sirtuin signaling contribute to impaired glucose and lipid metabolism, resulting in insulin resistance (IR) and endothelial dysfunction. Here, we examined the effects of palmitic acid (PA) treatment on mitochondrial sirtuins (SIRT2, SIRT3, SIRT4, and SIRT5) and oxidative homeostasis in human endothelial cells (TeloHAEC). Results showed that treatment for 48 h with PA (0.5 mM) impaired cell viability, induced loss of insulin signaling, imbalanced the oxidative status (p < 0.001), and caused negative modulation of sirtuin protein and mRNA expression, with a predominant effect on SIRT3 (p < 0.001). Restoration of SIRT3 levels by mimic transfection (SIRT3+) suppressed the PA-induced autophagy (mimic NC+PA) (p < 0.01), inflammation, and pyroptosis (p < 0.01) mediated by the NLRP3/caspase-1 axis. Moreover, the unbalanced endothelial redox state induced by PA was counteracted by the antioxidant δ-valerobetaine (δVB), which was able to upregulate protein and mRNA expression of sirtuins, reduce reactive oxygen species (ROS) accumulation, and decrease cell death. Overall, results support the central role of SIRT3 in maintaining the endothelial redox homeostasis under IR and unveil the potential of the antioxidant δVB in enhancing the defense against IR-related injuries.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…It can also regulate the activation and transplantation of signaling pathways such as NF-κB and AKT through the same mechanism, thereby regulating the production of adenosine triphosphate and infammatory factors, thereby participating in intracellular important physiological processes such as gene transcription, energy metabolism, and antioxidant defense that are important for maintaining the stability of the intracellular environment and normal pregnancy [13]. When the expression of sirtuins is downregulated, their protective efect is also weakened, which can induce abnormalities such as maintenance stress, excessive infammatory response, and energy metabolism disorders, leading to the occurrence of pathological pregnancy such as preeclampsia, GDM, and ICP [14]. In addition to being closely associated with the abovementioned pathological pregnancies such as spontaneous preterm birth, preeclampsia, GDM, ICP, and fetal growth restriction, the sirtuins family is also altered in other pathological pregnancies such as pregnancy depression and hyperemesis gravidarum.…”

Section: Introductionmentioning

confidence: 99%

[Retracted] Clinical Value of Serum SIRT1 Combined with Uterine Hemodynamics in Predicting Disease Severity and Fetal Growth Restriction in Preeclampsia

Kong

2023

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objective. The sirtuin regulator 1-related enzyme (SIRT1) has been shown to play an important role in various pathophysiological processes. Our aim was to investigate the effect and correlation of serum SIRT1 combined with uterine hemodynamic parameters on disease severity and fetal uterine growth restriction in the progression of preeclampsia and to evaluate its clinical value as a potential marker. Methods. A total of 100 patients with preeclampsia who were hospitalized in Qufu Normal University Hospital from June 2017 to June 2021 were selected as the research objects. According to the severity, they were divided into the mild (62 cases) and severe groups (38 cases), and according to whether the fetal growth restriction was combined or not, they were divided into the combined fetal growth restriction group (56 cases) and the uncomplicated fetal growth restriction group (44 cases). Serum SIRT1 expression and uterine artery hemodynamic parameters were detected, and Spearman analysis was used to evaluate the association of serum SIRT1 expression and uterine artery hemodynamic parameters (the peak-to-trough ratio of arterial blood velocity, the pulsatility index, and the resistance index) with disease severity (systolic blood pressure, diastolic blood pressure, and random urinary protein levels) and fetal growth restriction (femoral length, biparietal diameter, head circumference, and neonatal weight); unsupervised principal component analysis (PCA), supervised partial least-squares discrimination analysis (PLS-DA), cluster heat map analysis, the receiver operating characteristic (ROC) curve, and the area under curve (AUC) were used to evaluate the diagnostic value of serum SIRT1 expression combined with uterine artery hemodynamic parameters in the severity of disease and fetal growth restriction in patients with preeclampsia. Results. Compared with patients with mild preeclampsia, serum SIRT1 expression was lower in patients with severe preeclampsia ( p < 0.0001 ), the arterial blood flow velocity peak-to-trough ratio, pulsatility index, and resistance index were higher ( p < 0.001 ; p < 0.0001 ); and serum SIRT1 expression and uterine artery hemodynamic parameters were closely related to disease severity ( p < 0.001 ; p < 0.0001 ). In addition, the expression of serum SIRT1 in patients with preeclampsia combined with fetal growth restriction was lower than patients without preeclampsia ( p < 0.0001 ); the peak-to-trough ratio of arterial blood flow velocity, the pulsatility index, and the resistance index were higher ( p < 0.0001 ); and serum SIRT1 expression and uterine artery hemodynamics were closely related to fetal growth restriction ( p < 0.0001 ). Unsupervised PCA analysis and supervised PLS-DA analysis showed that patients with different severity of disease and patients with or without fetal growth restriction were similar within the groups, and there were significant differences between the groups; cluster heat map analysis showed that the mild and severe groups were stratified clustering, and the combined fetal growth restriction group and the uncombined group were hierarchically clustered; ROC curve showed that the AUC of serum SIRT1 expression combined with uterine artery hemodynamic parameters was 0.776 in identifying the severity of preeclampsia and 0.956 in identifying the preeclampsia complicated by fetal growth restriction. Conclusion. Serum SIRT1 combined with uterine hemodynamic parameters in preeclampsia is closely related to disease severity and fetal growth restriction and is expected to become a potential biomarker for early clinical intervention in patients.

show abstract

“…It also mediates resistance to FOLFOX and cetuximab via succinate accumulation and FOXO3a-induced apoptosis inhibition. SIRT5 modulation reduces CRC cell viability, especially in p53-expressing cells, suggesting its therapeutic potential 96 . SIRT5 orchestrates crucial metabolic and DNA integrity processes.…”

Section: Molecular Mechanisms Of Mitochondrial Sirtuins In Cancermentioning

confidence: 99%

Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies

Shen,

Ma,

et al. 2024

Theranostics

View full text Add to dashboard Cite

The sirtuin (SIRT) family is well-known as a group of deacetylase enzymes that rely on nicotinamide adenine dinucleotide (NAD + ). Among them, mitochondrial SIRTs (SIRT3, SIRT4, and SIRT5) are deacetylases located in mitochondria that regulate the acetylation levels of several key proteins to maintain mitochondrial function and redox homeostasis. Mitochondrial SIRTs are reported to have the Janus role in tumorigenesis, either tumor suppressive or oncogenic functions. Although the multi-faceted roles of mitochondrial SIRTs with tumor-type specificity in tumorigenesis, their critical functions have aroused a rising interest in discovering some small-molecule compounds, including inhibitors and activators for cancer therapy. Herein, we describe the molecular structures of mitochondrial SIRTs, focusing on elucidating their regulatory mechanisms in carcinogenesis, and further discuss the recent advances in developing their targeted small-molecule compounds for cancer therapy. Together, these findings provide a comprehensive understanding of the crucial roles of mitochondrial SIRTs in cancer and potential new therapeutic strategies.

show abstract

Mitochondrial Sirtuins in Chronic Degenerative Diseases: New Metabolic Targets in Colorectal Cancer

Cited by 10 publications

References 156 publications

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

[Retracted] Clinical Value of Serum SIRT1 Combined with Uterine Hemodynamics in Predicting Disease Severity and Fetal Growth Restriction in Preeclampsia

Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies

Contact Info

Product

Resources

About