AMPK activation suppresses mTOR/S6K1 phosphorylation and induces leucine resistance in rats with sepsis

Shi, Mengyao; Hu, Zunqi; Zhang, Xin; You, Qi; Wang, Weimin; Yan, Ran; Zhu, Zhenxin

doi:10.1002/cbin.11310

Cited by 7 publications

(4 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results indicated that the inhibition of MAGE‐A6 enhanced the radiosensitivity of non‐small cell lung cancer cells. On the other hand, the activation of AMPK inhibited the expression of p‐S6K1 31 . Upregulation of p‐S6K1 promoted the development of colorectal cancer 32 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Knockdown of MAGE‐A6 enhanced the irradiation sensitivity of non‐small cell lung cancer cells by activating the AMPK pathway

Zhou

Fan

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

Non-small cell lung cancer is a common respiratory tumor. The mortality rate of lung cancer patients has continued to rise in recent years. Several studies revealed that the expression of melanoma antigen 6 (MAGE-A6) promoted the development of multiple types of cancer. In addition, the suppression of AMPK pathway could restrict the radiosensitization of prostate cancer cells. Inhibition of MAGE-A6 activated the AMPK pathway in colorectal cancer cells. However, whether the MAGE-A6 could regulate the radiosensitivity of non-small cell lung cancer cells by regulating of the AMPK pathway is unclear. In this study, we established the MAGE-A6 knockdown in A549 and H1299 cells. Next, the apoptosis and proliferation of these cells were detected by the flow cytometry analysis and colony formation assay after the irradiation, respectively. Then, the expression of p-AMPKα1 and p-S6K1 in these cells was explored by the western blotting. After that, we inhibited the expression of AMPKα1 in MAGE-A6 knockdown cells. The proliferation and apoptosis of these cells were detected with colony formation assay and flow cytometry analysis. Finally, the tumor formation of these cells was detected in nude mice. Our results showed that inhibition of MAGE-A6 suppressed the proliferation and aggravated the apoptosis of A549 and H1299 cells after the irradiation. Knockdown of MAGE-A6 activated the expression of p-AMPKα1 and repressed the expression of p-S6K1 in these cells. Suppression of AMPKα1 in MAGE-A6 knockdown cells abolished these effects. Knockdown of MAGE-A6 also enhanced the radiosensitivity of these cells in vivo. These results suggested that inhibition of MAGE-A6 promoted the radiosensitivity of non-small cell lung cancer cells by activating AMPK pathway. Therefore, MAGE-6 has the potential to be explored as the therapeutic target for the treatment of non-small cell lung cancer in clinical.

show abstract

Section: Discussionmentioning

confidence: 99%

“…*p <.05, **p <.01, and ***p <.001cell lung cancer cells. On the other hand, the activation of AMPK inhibited the expression of p-S6K1 31. Upregulation of p-S6K1 promoted the development of colorectal cancer 32.…”

mentioning

confidence: 99%

Knockdown of MAGE‐A6 enhanced the irradiation sensitivity of non‐small cell lung cancer cells by activating the AMPK pathway

Zhou

Fan

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…In contrast, AMPK activates mTORC2 to enhance cell survival under nutrient stress [ 215 ]. AMPK dephosphorylates to inactivate mTOR and its downstream S6K1 and 4EBP1 [ 216 ]. AMPK is validated as upstream of SREBP.…”

Section: Akt Effectors Modulate Cell Functionsmentioning

confidence: 99%

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

et al. 2022

View full text Add to dashboard Cite

Oxidative stress and AKT serine-threonine kinase (AKT) are responsible for regulating several cell functions of cancer cells. Several natural products modulate both oxidative stress and AKT for anticancer effects. However, the impact of natural product-modulating oxidative stress and AKT on cell functions lacks systemic understanding. Notably, the contribution of regulating cell functions by AKT downstream effectors is not yet well integrated. This review explores the role of oxidative stress and AKT pathway (AKT/AKT effectors) on ten cell functions, including apoptosis, autophagy, endoplasmic reticulum stress, mitochondrial morphogenesis, ferroptosis, necroptosis, DNA damage response, senescence, migration, and cell-cycle progression. The impact of oxidative stress and AKT are connected to these cell functions through cell function mediators. Moreover, the AKT effectors related to cell functions are integrated. Based on this rationale, natural products with the modulating abilities for oxidative stress and AKT pathway exhibit the potential to regulate these cell functions, but some were rarely reported, particularly for AKT effectors. This review sheds light on understanding the roles of oxidative stress and AKT pathway in regulating cell functions, providing future directions for natural products in cancer treatment.

show abstract

“…This indicated that the effects of leucine might be different in different patients and this should be considered to better individualize nutrition to the critically ill. The second issue is that in animal models of sepsis there is a leucine resistance which is due to a high phosphorylation of AMPK which inhibits the activation of mTOR by leucine [12 ▪ ]. Whether this leucine resistance also exists in critically ill patient and if it possibly can be overcome by higher leucine dosage or HMB has not been investigated.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

HMB and leucine supplementation during critical illness and recovery

Bear

Rooyackers

2021

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

View full text Add to dashboard Cite

Purpose of reviewSkeletal muscle wasting is a serious consequence of critical illness, which may impact on long term physical and functional disability. To date, no intervention has been proven to reduce skeletal muscle wasting. Leucine and it's metabolite b-hydroxy-b-methylbutyrate (HMB) have been proposed as interventions. This review details the mechanism of action of both leucine and HMB, discusses the most recent research for both leucine and HMB and lastly discusses considerations for future research. Recent findingsOnly one study of leucine in critical illness has recently been published. This was a feasibility study where the physiological and muscle related outcomes were not reported to be feasible. Three studies on HMB have been reported recently with no effect seen on either muscle mass or strength. The main limitation in our understanding of the potential use of leucine or HMB on skeletal muscle wasting is the lack of mechanistic studies available in this population. SummaryMechanistic studies should be a priority before embarking on further randomized controlled trials related to this topic.

show abstract

AMPK activation suppresses mTOR/S6K1 phosphorylation and induces leucine resistance in rats with sepsis

Cited by 7 publications

References 28 publications

Knockdown of MAGE‐A6 enhanced the irradiation sensitivity of non‐small cell lung cancer cells by activating the AMPK pathway

Knockdown of MAGE‐A6 enhanced the irradiation sensitivity of non‐small cell lung cancer cells by activating the AMPK pathway

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

HMB and leucine supplementation during critical illness and recovery

Contact Info

Product

Resources

About