Honokiol attenuates oxidative stress-dependent heart dysfunction in chronic Chagas disease by targeting AMPK / NFE2L2 / SIRT3 signaling pathway

Caballero, Eugenia Pérez; Mariz-Ponte, Nilo; Rigazio, Cristina S.; Santamaría, Miguel H.; Corral, Ricardo S.

doi:10.1016/j.freeradbiomed.2020.05.024

Cited by 12 publications

(10 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STACs bind to the STAC-binding domain in the N terminus of SIRT1 and increase the binding affinity of a substrate for SIRT1 [ 151 ]. Honokiol is believed to be a specific SIRT3 activator, although it may also activate SIRT1 [ 16 , 152 ]. It is also necessary to implement the studies with cardiac-specific transgenic mice that inhibit the expression of SIRT1 and SIRT3 in combination with STACs in order to confirm the mechanisms of individual sirtuins.…”

Section: Discussionmentioning

confidence: 99%

“…SIRT1 can diminish oxidative stress by activating cardioprotective molecules and inhibit apoptosis-related signaling pathways against cardiac I/R [ 14 ]. Sirtuin3 (SIRT3), as the central control of mitochondrial protein deacetylation, protects cardiomyocytes from aging and oxidative stress [ 15 , 16 , 17 , 18 ]. SIRT3 deficiency aggravates the cardiac susceptibility to I/R stress with severe mitochondria abnormalities and exacerbates a higher level of myocardial I/R injury with aging [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SIRT1/SIRT3 Modulates Redox Homeostasis during Ischemia/Reperfusion in the Aging Heart

et al. 2020

View full text Add to dashboard Cite

Ischemia/reperfusion (I/R) injury is the central cause of global death in cardiovascular diseases, which is characterized by disorders such as angina, stroke, and peripheral vascular disease, finally causing severe debilitating diseases and death. The increased rates of morbidity and mortality caused by I/R are parallel with aging. Aging-associated cardiac physiological structural and functional deterioration were found to contribute to abnormal reactive oxygen species (ROS) production during I/R stress. Disturbed redox homeostasis could further trigger the related signaling pathways that lead to cardiac irreversible damages with mitochondria dysfunction and cell death. It is notable that sirtuin proteins are impaired in aged hearts and are critical to maintaining redox homeostasis via regulating substrate metabolism and inflammation and thus preserving cardiac function under stress. This review discussed the cellular and functional alterations upon I/R especially in aging hearts. We propose that mitochondria are the primary source of reactive oxygen species (ROS) that contribute to I/R injury in aged hearts. Then, we highlight the cardiomyocyte protection of the age-related proteins Sirtuin1 (SIRT1) and Sirtuin1 (SIRT3) in response to I/R injury, and we discuss their modulation of cardiac metabolism and the inflammatory reaction that is involved in ROS formation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SIRT1/SIRT3 Modulates Redox Homeostasis during Ischemia/Reperfusion in the Aging Heart

et al. 2020

View full text Add to dashboard Cite

show abstract

“… 2020 ) plays a critical role in chronic Chagas disease by targeting the AMPK/NFE2L2/SIRT3 signalling pathway (Caballero et al. 2020 ). In addition to these effects, SIRT3 is also known as a human longevity protein (Albani et al.…”

Section: Introductionmentioning

confidence: 99%

SIRT 3 was involved in Lycium barbarum seed oil protection testis from oxidative stress: in vitro and in vivo analyses

Zhou

Wang

Zhao

et al. 2021

Pharmaceutical Biology

View full text Add to dashboard Cite

Context Lycium barbarum L. (Solanaceae) seed oil (LBSO) exerts LBSO exerts protective effects in the testis in vivo and in vitro via upregulating SIRT3. Objective This study evaluates the effects and mechanism of LBSO in the d -galactose ( d -gal)-induced ageing testis. Materials and methods Male Sprague Dawley (SD) rats ( n = 30, 8-week-old) were randomly divided into three groups: LBSO group ( n = 10) where rats received subcutaneous injection of d -gal at 125 mg/kg/day for 8 weeks and intragastric administration of LBSO at 1000 mg/kg/day for 4 weeks, ageing model group ( n = 10) received 8-week-sunbcutaneous injection of d -gal, and control group ( n = 10) with same administration of normal saline. Lentivirus had established TM4 cells with SIRT3 overexpression or silencing before LBSO intervened in vitro . Results Treatment with LBSO, the levels of INHB and testosterone both increased, compared to ageing model. In vitro , we found the ED 50 of LBSO was 86.72 ± 1.49 and when the concentration of LBSO at 100 μg/mL to intervene TM4 cells, the number of cells increased from 8120 ± 676.2 to 15251 ± 1119, and the expression of SIRT3, HO-1, and SOD upregulated. However, HO-1 and SOD were dysregulated by silencing SIRT3. On the other hand, the expression of AMPK and PGC-1 α upregulated as an effect of SIRT3 overexpression by lentivirus, meanwhile the same increasing trend of that being found in cells treated with LBSO, compared to control group. Discussion and conclusions LBSO alleviated oxidative stress in d -gal-induced sub-acutely ageing testis and TM4 cells by suppressing the oxidative stress to mitochondria via SIRT3/AMPK/PGC-1α.

show abstract

“…HK acts as an activator of SIRT3 to reverse cardiac hypertrophy and alleviate oxidative stress [19][20][21]. Additionally, the binding of HK and SIRT3 activates AMPK to regulate in cellular energy homeostasis [20]. These ndings suggest a possible role of HK in regulating hepatic lipid homeostsis.…”

Section: Introductionmentioning

confidence: 98%

“…HK was demonstrated to alleviate hepatic steatosis in various models [15][16][17][18]. HK acts as an activator of SIRT3 to reverse cardiac hypertrophy and alleviate oxidative stress [19][20][21]. Additionally, the binding of HK and SIRT3 activates AMPK to regulate in cellular energy homeostasis [20].…”

Section: Introductionmentioning

confidence: 99%

Honokiol Attenuates Lipotoxicity in Hepatocytes via Activating SIRT3-AMPK Mediated Lipophagy

Zhang

Liu

Zhu

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic accumulation of triglycerides in the liver. Emerging evidence has demonstrated that lipophagy regulates lipid mobilization and energy homeostasis in liver. Sirtuin 3 (SIRT3), a mitochondrial NAD+-dependent deacetylase, modulates the activities of several substrates involving in autophagy and energy metabolism. Honokiol (HK) is a natural lignan from the plants of Magnolia genus that exhibits potent liver protective property. Methods: AML12 was challenged with 500 μM palmitic acid and 250 μM oleic acid mixture solution to induce lipotoxicity. The expression of autophagy-related and AMP-activated protein kinase (AMPK) pathway proteins was evaluated by Western blotting and immunofluorescence staining. Intracellular lipid accumulation was validated by Nile red staining. Molecular docking analysis was performed on AutoDock 4.2.Results: HK (5 and 10 μM) was found to attenuate lipid accumulation through promoting SIRT3-AMPK-mediated autophagy, mainly on lipid droplets. HK had hydrophobic interaction with amino acid residues (PHE294, GLU323 and VAL324) and NAD+. Moreover, HK improved mitochondrial function to enhance lipolysis, through decreasing the acetylated long-chain acyl-CoA dehydrogenase level. Conclusions: These results suggest that HK could ameliorate lipotoxicity in hepatocytes by activating SIRT3-AMPK-lipophagy axis, which might be a potential therapeutic agent against NAFLD.

show abstract

Honokiol attenuates oxidative stress-dependent heart dysfunction in chronic Chagas disease by targeting AMPK / NFE2L2 / SIRT3 signaling pathway

Cited by 12 publications

References 55 publications

SIRT1/SIRT3 Modulates Redox Homeostasis during Ischemia/Reperfusion in the Aging Heart

SIRT1/SIRT3 Modulates Redox Homeostasis during Ischemia/Reperfusion in the Aging Heart

SIRT 3 was involved in Lycium barbarum seed oil protection testis from oxidative stress: in vitro and in vivo analyses

Honokiol Attenuates Lipotoxicity in Hepatocytes via Activating SIRT3-AMPK Mediated Lipophagy

Contact Info

Product

Resources

About