Sirtuins play critical and diverse roles in acute kidney injury

Peasley, Kevin; Chiba, Takuto; Goetzman, Eric S.; Sims‐Lucas, Sunder

doi:10.1007/s00467-020-04866-z

Cited by 12 publications

(5 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Approximately 25% of cardiac output passes through the kidneys. Therefore, drugs can damage the kidneys and have potentially toxic effects (Peasley et al 2021).…”

Section: Discussionmentioning

confidence: 99%

Carvacrol attenuates amikacin-induced nephrotoxicity in the rat

Dost

Gunata

Özhan

et al. 2021

Preprint

View full text Add to dashboard Cite

Amikacin (AK) is frequently used in the treatment of gram-negative and some gram-positive infections. However, its use is limited due to nephrotoxicity due to the increase in reactive oxygen radicals. The aim of this study was to investigate the role of carvacrol (CAR) against AK-induced nephrotoxicity in rats. Thirty-two Sprague Dawley rats were randomly divided into four groups as control (Vehicle), AK (400 mg/kg), CAR + AK (80 mg/kg CAR + 400 mg/kg AK), and AK + CAR (400 mg/kg AK + 80 mg/kg CAR) groups. AK and CAR were administered via intramuscular and per-oral for 7 days, respectively. Blood and kidney tissue samples were taken at the end of the experiment. Renal function and histopathological changes were compared, and the relevant parameters of oxidative stress and inflammation were detected. Histopathological findings (necrotic changes and dilatation and inflammatory cell infiltration) significantly increased in the AK group compared to the control group. Also, the rats in the AK group lost weight significantly. It was found that CAR treatment before and after AK significantly improved nephrotoxicity histopathologically (p < 0.05). However, this improvement was not detected biochemically. These results show that CAR treatment before and after AK improves nephrotoxicity in the histopathological level.

show abstract

“…Approximately 25% of cardiac output passes through the kidneys. Therefore, drugs can damage the kidneys and have potentially toxic effects (Peasley et al 2021).…”

Section: Discussionmentioning

confidence: 99%

Carvacrol attenuates amikacin-induced nephrotoxicity in the rat

Dost

Gunata

Özhan

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Subsequently, this translocation promotes the transcription of inflammation-related genes [92]. However, research has revealed that silent information regulator transcript 1 (SIRT1), also known as Sirtuin1, has the potential to mitigate kidney injury [93]. SIRT1 is a histone deacetylase, and overexpressing SIRT1 in renal TECs inhibits NF-κB activation.…”

Section: Inflammationmentioning

confidence: 99%

From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease

Yeh,

Tu,

Wang

et al. 2024

IJMS

View full text Add to dashboard Cite

This article provides a thorough overview of the biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI) and acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical applications. This review also highlights the links between renal injury and the pathophysiological mechanisms underlying AKI and AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and the cellular senescence of renal cells. Key signaling pathways, such as Wnt/β-catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The renin–angiotensin–aldosterone system (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating the oxidative stress and cellular changes that promote fibrosis. The clinical evidence suggests that RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.

show abstract

“…Loss of sirt5 leads to decreased β-OHB production (19). Although its role in AKI is relatively controversial (46)(47)(48)(49), sirt5 still serves as a global regulator of lysine succinylation in mitochondria and mediates ketogenesis through Hmgcs2. Of note, sirt3 is responsible for global protein deacetylation in mitochondria.…”

Section: Jcimentioning

confidence: 99%

Calponin 2 regulates ketogenesis to mitigate acute kidney injury

Gui,

Palanza,

Gupta

et al. 2023

JCI Insight

View full text Add to dashboard Cite

Calponin 2 (CNN2) is a prominent actin stabilizer. It regulates fatty acid oxidation (FAO) by interacting with estrogen receptor 2 (ESR2) to determine kidney fibrosis. However, whether CNN2 is actively involved in acute kidney injury (AKI) remains unclear. Here, we report that CNN2 was induced in human and animal kidneys after AKI. Knockdown of CNN2 preserved kidney function, mitigated tubular cell death and inflammation, and promoted cell proliferation. Distinct from kidney fibrosis, proteomics showed that the key elements in the FAO pathway had few changes during AKI, but we identified that 3-hydroxymethylglutaryl-CoA synthase 2 (Hmgcs2), a rate-limiting enzyme of endogenous ketogenesis that promotes cell self-renewal, was markedly increased in CNN2-knockdown kidneys. The production of ketone body β-hydroxybutyrate and ATP was increased in CNN2-knockdown mice. Mechanistically, CNN2 interacted with ESR2 to negatively regulate the activities of mitochondrial sirtuin 5. Activated sirtuin 5 subsequently desuccinylated Hmgcs2 to produce energy for mitigating AKI. Understanding CNN2-mediated discrete fine-tuning of protein posttranslational modification is critical to optimize organ performance after AKI.

show abstract

Sirtuins play critical and diverse roles in acute kidney injury

Cited by 12 publications

References 89 publications

Carvacrol attenuates amikacin-induced nephrotoxicity in the rat

Carvacrol attenuates amikacin-induced nephrotoxicity in the rat

From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease

Calponin 2 regulates ketogenesis to mitigate acute kidney injury

Contact Info

Product

Resources

About