China
Africa
Explore chapters and articles related to this topic
Molecular Mechanisms of Brain Insulin Signaling 1
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Simran Chopra, Robert Hauffe, André Kleinridders
Moreover, insulin-induced AKT activation is crucial to modulate gene regulation via blocking the activity of FOXO transcription factors. There are four members of the FOXO family which include FOXO1, FOXO3, FOXO4, and FOXO6, where FOXO1 and FOXO3 are expressed in almost all tissues. AKT phosphorylates FOXO proteins at several serine residues (50) which facilitates the binding of FOXOs to proteins of the 14-3-3 family. This interaction leads to the nuclear exclusion of FOXO proteins and inhibition of their transcriptional activity (50). It has been suggested that the FOXO1 function is an important regulator of food intake and energy balance (51). While insulin inhibits FOXO1 activity and reduces food intake, active FOXO1 enhances food intake. FOXO6 is primarily expressed in the hippocampus of the brain and liver. It has been observed that upon whole-body deletion of FOXO6, although the mice exhibited normal learning behavior, they displayed impaired memory consolidation. In addition, through the process of stereotactic injection of viruses into the hippocampus of wild-type adult mice, it was revealed that FOXO6 activity in the hippocampus was important to promote memory consolidation (52, 53), indicating that insulin action can affect memory via FOXO6 regulation.
Isoflurane alleviates hypoxia/reoxygenation induced myocardial injury by reducing miR-744 mediated SIRT6
Published in Toxicology Mechanisms and Methods, 2022
Guoqing Chen, Faqiang Zhang, Long Wang, Zeguo Feng
As we all know, miRNA plays a role by regulating targets, so we tried to explore the target that miR-744 involved in ISO pretreatment to protect cardiomyocytes from H/R myocardial injury. Online biological software found that SIRT6 has a binding site with miR-744, and the luciferase report assay showed that miR-744 mimic down-regulate SIRT6-WT luciferase activity, confirming that SIRT6 is a direct target of miR-744. SIRT6 is one of seven members of the NAD (+)-dependent histone deacetylase family of sirtuins, which promotes resistance to DNA damage and oxidative stress by enhancing DNA double-strand break repair. Studies have found that polydatin can reduce the myocardial injury caused by sepsis by regulating the autophagy response mediated by SIRT6 (Yuan et al. 2020). FOXO6 participates in hypoxia-induced myocardial cell injury by upregulating SIRT6 (Jin et al. 2020). SIRT6 deficiency-induced cardiac dysfunction and fibrosis in mice (Maity et al. 2020). In the current study, we found that H/R remarkedly reduced the m RNA level of SIRT6, whereas ISO pretreatment significantly restored the mRNA level, which was contrary to miR-744. However, its specific role still needs further study. The results of this study should be interpreted with consideration of the following limitations. Such as we simulated clinical patients undergoing ISO anesthesia before ischemia-reperfusion, so this study only focused on the study before ISO preconditioning.
Targeting Autophagy In Disease: Recent Advances In Drug Discovery
Published in Expert Opinion on Drug Discovery, 2020
Dasol Kim, Hui-Yun Hwang, Ho Jeong Kwon
FoxO transcription factor family members (FoxO1, FoxO3, FoxO4, and FoxO6) have established roles in diverse cellular functions such as aging, longevity, and development [30]. Similar to the MiT/TFE family, the FoxO transcription factor family is mostly controlled by phosphorylation [31]. AKT/JNK kinase signaling is a major upstream regulator for FoxO1, FoxO3, and FoxO4, but less for FoxO6 due to its lack of a C-terminal AKT-dependent site [30,32]. Among these, FoxO3 [33] and FoxO1 [34] were reported to be autophagy gene transcription factors. A recent study exhibited the relevance of FoxO4 to autophagy gene expression through a triple genetic deletion of FoxO1, FoxO3, and FoxO4 in muscle [35]. However, it is currently unclear whether FoxO4 binds directly to the promoter region of autophagy genes. The FoxO family is regarded as another pivotal modulator for cellular homeostasis through autophagy, as these members have central roles in diverse diseases.
The protective effect of beta-casomorphin-7 via promoting Foxo1 activity and nuclear translocation in human lens epithelial cells
Published in Cutaneous and Ocular Toxicology, 2018
Lihua Zhu, Jia Li, Dayang Wu, Bing Li
The Foxo family of transcription factors includes Foxo1, Foxo3a, Foxo4, and Foxo6 in mammal9. Foxos are ubiquitously expressed10. Foxo proteins play a crucial role as transcriptional activators and are involved in a wide range of cellular processes that regulate metabolism, apoptosis, and cellular oxidative stress responses11–13. Foxo1 was one of the earliest known members of the Foxo family. Also, Foxo1 plays as a crucial protective role in multiple cellular processes, such as antioxidative responses, when activated and transferred to the nucleus. Increased Foxo1 activities and mutual combination with other proteins that are associated with cellular activity, such as the cell cycle, DNA repair, oxidative stress, and apoptosis, enhance the transcription activity of Foxo1, against oxidative stress14–16. The cell’s oxidative state induces nuclear localization of Foxo members. The ability of Foxo1 to resist oxidative damage by nuclear translation has been confirmed. However, hyperglycaemic-induced oxidative stress in HLECs has not been proven.