Energy sensing factors PGC-1α and SIRT1 modulate PXR expression and function

Buler, Marcin; Aatsinki, Sanna Mari; Skoumal, Réka; Hakkola, Jukka

doi:10.1016/j.bcp.2011.09.006

Cited by 44 publications

(35 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although this speculation needs to be tested, it is a likely scenario because increased pyruvate is known to activate SIRT1 (40), but SIRT1 expression is decreased after T-H. Importantly, the role of SIRT1 in activation/inactivation of PDK1 is unknown.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Restores Sirtuin 1 (SIRT1) Activity and Pyruvate Dehydrogenase Kinase 1 (PDK1) Expression after Hemorrhagic Injury in a Rat Model

Jian

Yang

Chaudry

et al. 2013

Mol Med

View full text Add to dashboard Cite

Severe hemorrhage leads to decreased blood flow to tissues resulting in decreased oxygen and nutrient availability affecting mitochondrial function. A mitoscriptome profiling study demonstrated alteration in several genes related to mitochondria, consistent with the mitochondrial functional decline observed after trauma hemorrhage (T-H). Our experiments led to the identification of sirtuin 1 (SIRT1) as a potential target in T-H. Administration of resveratrol (a naturally occurring polyphenol and activator of SIRT1) after T-H improved left ventricular function and tissue ATP levels. Our hypothesis was that mitochondrial function after T-H depends on SIRT1 activity. In this study, we evaluated the activity of SIRT1, a mitochondrial functional modulator, and the mitochondrialglycolytic balance after T-H. We determined the changes in protein levels of pyruvate dehydrogenase kinase (PDK)-1 and nuclear c-Myc, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and NF-E2-related factor (NRF)2 after T-H and after treatment with resveratrol or a combination of sirtinol (a SIRT1 inhibitor) and resveratrol. We have also tested the activity of mitochondrial complex 1. SIRT1 enzyme activity was significantly decreased after T-H, whereas resveratrol treatment restored the activity. We found elevated PDK1 and c-Myc levels and decreased PGC-1α, NRF2 and mitochondrial complex I activity after T-H. The reduced SIRT1 activity after T-H may be related to declining mitochondrial function, since resveratrol was able to reinstate SIRT1 activity and mitochondrial function. The elevated level of PDK1 (an inhibitor of pyruvate dehydrogenase complex) after T-H indicates a possible shift in cellular energetics from mitochondria to glycolysis. In conclusion, SIRT1 modulation alters left ventricular function after T-H through regulation of cellular energetics.

show abstract

Section: Discussionmentioning

confidence: 99%

Resveratrol Restores Sirtuin 1 (SIRT1) Activity and Pyruvate Dehydrogenase Kinase 1 (PDK1) Expression after Hemorrhagic Injury in a Rat Model

Jian

Yang

Chaudry

et al. 2013

Mol Med

View full text Add to dashboard Cite

show abstract

“…Interestingly, short-term fasting increases the activity of both constitutive androstane receptor (CAR) and PXR (Ding et al, 2006;Hernandez et al, 2009). However, the mechanisms regulating nuclear transcription factors are complex, and fasting can also attenuate PXR function, as studied by Buler et al (2011). Because the activities of CAR and PXR are altered by fasting and both transcription factors are involved in the regulation of drug metabolism in animals, we hypothesized that short-term fasting influences drug metabolism in humans as well.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Fasting Alters Cytochrome P450–Mediated Drug Metabolism in Humans

et al. 2015

View full text Add to dashboard Cite

Experimental studies indicate that short-term fasting alters drug metabolism. However, the effects of short-term fasting on drug metabolism in humans need further investigation. Therefore, the aim of this study was to evaluate the effects of short-term fasting (36 h) on P450-mediated drug metabolism. In a randomized crossover study design, nine healthy subjects ingested a cocktail consisting of five P450-specific probe drugs [caffeine (CYP1A2), S-warfarin (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6), and midazolam (CYP3A4)] on two occasions (control study after an overnight fast and after 36 h of fasting). Blood samples were drawn for pharmacokinetic analysis using nonlinear mixed effects modeling. In addition, we studied in Wistar rats the effects of short-term fasting on hepatic mRNA expression of P450 isoforms corresponding with the five studied P450 enzymes in humans. In the healthy subjects, short-term fasting increased oral caffeine clearance by 20% (P = 0.03) and decreased oral S-warfarin clearance by 25% (P < 0.001). In rats, short-term fasting increased mRNA expression of the orthologs of human CYP1A2, CYP2C19, CYP2D6, and CYP3A4 (P < 0.05), and decreased the mRNA expression of the ortholog of CYP2C9 (P < 0.001) compared with the postabsorptive state. These results demonstrate that short-term fasting alters cytochrome P450-mediated drug metabolism in a nonuniform pattern. Therefore, short-term fasting is another factor affecting cytochrome P450-mediated drug metabolism in humans.

show abstract

“…Along with gluconeogenic genes, fasting induces transcription of some genes involved in biotransformation (e.g., Cyp2b10, CYP2C11, CYP2E1, CYP2B1/2) and transport (e.g., Slco1b2) in coordination with nuclear receptors (6,9). However, little is known about effect of nutritional status on biliary clearance mechanisms or bile flow.…”

mentioning

confidence: 99%

Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

Kulkarni

Donepudi

et al. 2014

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Aims: The purpose of this study was to determine whether 3¢-5¢-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2-4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2-and SIRT1-dependent mechanisms. In intact mouse liver, fasting induces NRF2 target gene expression by at least 1.5 to 5-fold. In mouse and human hepatocytes, treatment with 8-Bromoadenosine-cAMP, a cAMP analogue, increased NRF2 target gene expression and antioxidant response element activity, which was decreased by the PKA inhibitor, H-89. Moreover, fasting induced NRF2 target gene expression was decreased in liver and hepatocytes of SIRT1 liver-specific null mice and NRF2-null mice. Lastly, NRF2 and SIRT1 were recruited to MAREs and Antioxidant Response Elements (AREs) in the human ABCC2 promoter. Innovation: Oxidative stress mediated NRF2 activation is well described, yet the influence of basic metabolic processes on NRF2 activation is just emerging. Conclusion: The current data point toward a novel role of nutrient status in regulation of NRF2 activity and the antioxidant response, and indicates that cAMP/PKA and SIRT1 are upstream regulators for fasting-induced activation of the NRF2-ARE pathway. Antioxid. Redox Signal. 20,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]

show abstract

Energy sensing factors PGC-1α and SIRT1 modulate PXR expression and function

Cited by 44 publications

References 31 publications

Resveratrol Restores Sirtuin 1 (SIRT1) Activity and Pyruvate Dehydrogenase Kinase 1 (PDK1) Expression after Hemorrhagic Injury in a Rat Model

Resveratrol Restores Sirtuin 1 (SIRT1) Activity and Pyruvate Dehydrogenase Kinase 1 (PDK1) Expression after Hemorrhagic Injury in a Rat Model

Short-Term Fasting Alters Cytochrome P450–Mediated Drug Metabolism in Humans

Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

Contact Info

Product

Resources

About