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AMPK activator-treated human cardiac spheres have enhanced maturation and enable pathological modeling

ABSTRACT: AMPK activator-treated human cardiac spheres have enhanced maturation and enable pathological modeling

PROVIDER: PRJNA840926 | ENA |

REPOSITORIES: ENA

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AMPK activator-treated human cardiac spheres have enhanced maturation and enable pathological modeling

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NRF2 activator-treated human cardiac spheres have enhanced maturation and enable disease modeling

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AMPK activator O304 protects against kidney aging through promoting energy metabolism and autophagy

Project description:Energy homeostasis plays a key role in retarding aging, and mitochondria are responsible for energy production.AMPK plays a central role in maintaining energy homeostasis and mitochondrial homeostasis, and commands autophagy, a clearing and recycling process to maintain cellular homeostasis. However, the effect of AMPK activators on kidney aging has not been fully elucidated. We testified the effects of O304, a novel direct AMPK activator, in naturally aging mice model and D-galactose (D-gal)-treated renal tubular cell culture. We identified that O304 perfectly protects against cellular senescence and aged-related fibrosis in kidneys. Also, O304 restored energy metabolism, promoted autophagy, and preserved mitochondrial homeostasis. Transcriptomic sequencing also proved that O304 induced fatty acid metabolism, mitochondrial biogenesis and ATP process, and downregulated cell aging, DNA damage response and collagen organization. All these results suggest that O304 has a strong potential to retard aged kidney injury through regulating AMPK-induced multiple pathways.

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AMPK activation exerts anti-senescence effect in human follicle dermal papilla cells

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AMPK activator 991 specifically activates SnRK1 and thereby affects seed germination in rice

Project description:Sucrose non-fermenting-1-related protein kinase 1 (SnRK1) is a central regulator of metabolism and developmental transition in plant. Compound 991 is a well-known 5′-adenosine monophosphate activated protein kinase (AMPK) activator in mammals. SnRK1 and AMPK are highly conserved. However, whether 991 could also act as a SnRK1 activator is unknown. Adding 991 significantly increased the activity of SnRK1 in desalted extracts from germinating rice seeds in vitro. To determine whether 991 has biological activity in plant, rice seeds were treated with different concentrations of 991. Low concentration of 991 promoted rice seed germination, while high concentration of 991 inhibited rice germination. The effect of 991 on rice germination is similar to the effect of OsSnRK1a overexpression on germination. To explore whether 991 affects germination by specifically affecting SnRK1, the germination status of the snrk1a mutant and WT under 1 μM 991 treatment were compared. The snrk1a mutant exhibited insensitivity to 991. Through phosphoproteomic analysis, we found that the differential phosphopeptides caused by 991 treatments and overexpression of OsSnRK1a are largely overlapped. Phosphoproteomic analysis also revealed that SnRK1 might affect rice germination by regulating the phosphorylation levels of S285-PIP2;4, S1013-SOS1 and S110-ABI5. These results showed that 991 is a specific and workable SnRK1 activator in rice. The promotion and inhibition of 991 treatments on germination also exist in wheat seeds. 991 is expected to be used for exploring the function of SnRK1 in more detail and depth and chemical regulation of growth and development in crops.

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AMPK activation exerts anti-senescence effect in human follicle dermal papilla cells

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A new LKB1 activator, Piericidin Analogue S14, attenuates tubular cell senescence and renal fibrosis through promoting AMPK-induced autophagy and mitochondrial homeostasis pathway [II]

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