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1.
EMBO Rep ; 25(3): 1055-1074, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38351372

RESUMO

Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. However, the molecular basis for HSC activation remains poorly understood. Herein, we demonstrate that primary cilia are present on quiescent HSCs but exhibit a significant loss upon HSC activation which correlates with decreased levels of the ciliary protein intraflagellar transport 88 (IFT88). Ift88-knockout mice are more susceptible to chronic carbon tetrachloride-induced liver fibrosis. Mechanistic studies show that the X-linked inhibitor of apoptosis (XIAP) functions as an E3 ubiquitin ligase for IFT88. Transforming growth factor-ß (TGF-ß), a profibrotic factor, enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-ß-induced HSC activation and liver fibrosis. These findings reveal a previously unrecognized role for ciliary homeostasis in regulating HSC activation and identify the XIAP-IFT88 axis as a potential therapeutic target for liver fibrosis.


Assuntos
Cílios , Cirrose Hepática , Animais , Camundongos , Cílios/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fator de Crescimento Transformador beta/metabolismo
2.
Acta Pharmacol Sin ; 45(3): 449-464, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37993536

RESUMO

As the hub of cellular lipid metabolism, lipid droplets (LDs) have been linked to a variety of biological processes. During pathogen infection, the biogenesis, composition, and functions of LDs are tightly regulated. The accumulation of LDs has been described as a hallmark of pathogen infection and is thought to be driven by pathogens for their own benefit. Recent studies have revealed that LDs and their subsequent lipid mediators contribute to effective immunological responses to pathogen infection by promoting host stress tolerance and reducing toxicity. In this comprehensive review, we delve into the intricate roles of LDs in governing the replication and assembly of a wide spectrum of pathogens within host cells. We also discuss the regulatory function of LDs in host immunity and highlight the potential for targeting LDs for the diagnosis and treatment of infectious diseases.


Assuntos
Gotículas Lipídicas , Lipídeos , Metabolismo dos Lipídeos
3.
Int J Mol Sci ; 25(13)2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38999988

RESUMO

The orchestration of cellular metabolism and redox balance is a complex, multifaceted process crucial for maintaining cellular homeostasis. Lipid droplets (LDs), once considered inert storage depots for neutral lipids, are now recognized as dynamic organelles critical in lipid metabolism and energy regulation. Mitochondria, the powerhouses of the cell, play a central role in energy production, metabolic pathways, and redox signaling. The physical and functional contacts between LDs and mitochondria facilitate a direct transfer of lipids, primarily fatty acids, which are crucial for mitochondrial ß-oxidation, thus influencing energy homeostasis and cellular health. This review highlights recent advances in understanding the mechanisms governing LD-mitochondria interactions and their regulation, drawing attention to proteins and pathways that mediate these contacts. We discuss the physiological relevance of these interactions, emphasizing their role in maintaining energy and redox balance within cells, and how these processes are critical in response to metabolic demands and stress conditions. Furthermore, we explore the pathological implications of dysregulated LD-mitochondria interactions, particularly in the context of metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease, and their potential links to cardiovascular and neurodegenerative diseases. Conclusively, this review provides a comprehensive overview of the current understanding of LD-mitochondria interactions, underscoring their significance in cellular metabolism and suggesting future research directions that could unveil novel therapeutic targets for metabolic and degenerative diseases.


Assuntos
Gotículas Lipídicas , Metabolismo dos Lipídeos , Mitocôndrias , Humanos , Gotículas Lipídicas/metabolismo , Mitocôndrias/metabolismo , Animais , Metabolismo Energético , Oxirredução , Doenças Metabólicas/metabolismo , Homeostase
4.
J Cell Physiol ; 238(11): 2638-2650, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37683043

RESUMO

Skeletal muscle regeneration is a crucial physiological process that occurs in response to injury or disease. As an important transcriptome surveillance system that regulates tissue development, the role of nonsense-mediated mRNA decay (NMD) in muscle regeneration remains unclear. Here, we found that NMD inhibits myoblast differentiation by targeting the phosphoinositide-3-kinase regulatory subunit 5 gene, which leads to the suppression of the transcriptional activity of myogenic differentiation (MyoD), a key regulator of myoblast differentiation. This disruption of MyoD transcriptional activity subsequently affects the expression levels of myogenin and myosin heavy chain, crucial markers of myoblast differentiation. Additionally, through up-frameshift protein 1 knockdown experiments, we observed that inhibiting NMD can accelerate muscle regeneration in vivo. These findings highlight the potential of NMD as a novel therapeutic target for the treatment of muscle-related injuries and diseases.


Assuntos
Mioblastos , Degradação do RNAm Mediada por Códon sem Sentido , Animais , Masculino , Camundongos , Diferenciação Celular/genética , Linhagem Celular , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismo , Músculos , Mioblastos/metabolismo , Proteína MyoD/genética , Proteína MyoD/metabolismo , Miogenina/genética , Miogenina/metabolismo , Degradação do RNAm Mediada por Códon sem Sentido/genética
5.
J Cell Physiol ; 238(11): 2600-2611, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37683035

RESUMO

The primary cilium is increasingly recognized as a crucial player in the physiology of biliary epithelial cells (BECs). However, the precise role of primary cilia in the development of age-related biliary fibrosis remains unclear. Herein, using cilium-deficient mice, we demonstrate that disruption of ciliary homeostasis in BECs in aged mice leads to significant bile duct proliferation, augmented biliary fibrosis, and heightened indicators of liver injury. Our RNA-sequencing data revealed a dysregulation in genes associated with various biological processes such as bile secretion, fatty acid metabolism, and inflammation. Loss of primary cilia also significantly enhanced signaling pathways driving the development of biliary fibrosis. Our findings collectively suggest that loss of primary cilia in the BECs of aged mice initiates a cascade of signaling events that contribute to biliary fibrosis, highlighting the primary cilium as a potential therapeutic target in the treatment of fibrosing cholangiopathies.


Assuntos
Cílios , Hepatopatias , Animais , Camundongos , Cílios/metabolismo , Hepatopatias/metabolismo , Células Epiteliais/metabolismo , Fibrose
6.
J Muscle Res Cell Motil ; 44(1): 11-23, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36512272

RESUMO

Nonsense mediated mRNA decay (NMD) is a highly conserved RNA quality control system, which can specifically clear abnormal mRNA and play an important role in tumorigenesis. Myoblast proliferation plays an important role in the repair of skeletal muscle injury and the development of myosarcoma, and is controlled by a variety of transcription factors and signals. The molecular mechanism by which NMD regulates the proliferation of myoblast cells is not completely clear. In this study, we found that the NMD activity of skeletal muscle is high in 1-week-old mice but decreases gradually with age, corresponding to a weakening capacity for muscle growth and regeneration. Here, we provide evidence that NMD plays an important role in myoblast proliferation and apoptosis. In addition, we found that PIK3R5 is an NMD substrate gene which can inhibit AKT activity and C2C12 cell proliferation. Therefore, NMD can target PIK3R5 to enhance AKT activity, which in turn promotes C2C12 cell proliferation. This study provides new insights into NMD regulatory mechanisms in muscular development and into potential novel therapeutic strategies for muscle atrophy.


Assuntos
Degradação do RNAm Mediada por Códon sem Sentido , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Fatores de Transcrição/genética , Proliferação de Células
7.
Int J Mol Sci ; 24(9)2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37176077

RESUMO

Oxidative stress (OS) arises as a consequence of an imbalance between the formation of reactive oxygen species (ROS) and the capacity of antioxidant defense mechanisms to neutralize them. Excessive ROS production can lead to the damage of critical biomolecules, such as lipids, proteins, and DNA, ultimately contributing to the onset and progression of a multitude of diseases, including atherosclerosis, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer. Cylindromatosis (CYLD), initially identified as a gene linked to familial cylindromatosis, has a well-established and increasingly well-characterized function in tumor inhibition and anti-inflammatory processes. Nevertheless, burgeoning evidence suggests that CYLD, as a conserved deubiquitination enzyme, also plays a pivotal role in various key signaling pathways and is implicated in the pathogenesis of numerous diseases driven by oxidative stress. In this review, we systematically examine the current research on the function and pathogenesis of CYLD in diseases instigated by oxidative stress. Therapeutic interventions targeting CYLD may hold significant promise for the treatment and management of oxidative stress-induced human diseases.


Assuntos
Estresse Oxidativo , Transdução de Sinais , Humanos , Enzima Desubiquitinante CYLD/genética , Enzima Desubiquitinante CYLD/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Oxirredução
8.
BMC Cardiovasc Disord ; 22(1): 471, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348283

RESUMO

BACKGROUND: Chronic heart failure (CHF) is characterized by a high hospitalization rate and a high mortality rate. It is particularly important to identify biomarkers for predicting the prognosis of patients with acute attack of CHF. PURPOSE: To observe the correlation between galectin-3, RDW, Hepc, HS and ferritin and the prognosis of patients with acute onset of CHF. METHODS: The study included 92 patients with acute onset of CHF who received treatment at our hospital between August 2020 and December 2021. After treatment, the patients were divided into the effective group and the non-effective group based on the effectiveness of treatment. The levels of galectin-3, RDW, Hepc, HS and ferritin before and after treatment were compared between the two groups and the correlation between prognosis of patients with acute attack of CHF and galectin-3, RDW, Hepc, HS and ferritin was observed. RESULTS: The effective rate was 71.74% (66/92) and the ineffective rate was 28.26% (26/92) in the 92 patients with acute attack of CHF in the study. Before and after treatment, the levels of galectin-3, RDW, Hepc, and HS were lower in the effective group than those of the non-effective group while the level of ferritin was higher in the effective group than that of the non-effective group (P < 0.05). Spearman correlation analysis showed that the level of prognosis of patients with acute attack of CHF was positively correlated with galectin-3, RDW, Hepc, and HS (r = 0.217, 0.109, 0.376, 0.765, P = 0.026, 0.032, 0.021, 0.006), and negatively correlated with ferritin (r = - 0.127, P = 0.037). The independent variables were galectin-3, RDW, Hepc, HS and ferritin and the dependent variable was prognosis of patients with acute attack of CHF. Univariate logistic regression analysis showed that alectin-3, RDW, Hepc, HS, and ferritin were protective factors for the prognosis of patients with acute attack of CHF. The independent variables were galectin-3, RDW, Hepc, HS and ferritin, dependent variables and the dependent variable was prognosis of patients with acute attack of CHF. Multivariate logistic regression analysis revealed that galectin-3, RDW, and Hepc were risk factors of the prognosis of patients with acute attack of CHF. CONCLUSION: Galectin-3, RDW, Hepc, HS and ferritin were closely related with the prognosis of patients with acute attack of CHF and galectin-3, RDW, and Hepc were risk factors of the prognosis of patients with acute attack of CHF.


Assuntos
Galectina 3 , Insuficiência Cardíaca , Humanos , Doença Crônica , Índices de Eritrócitos , Ferritinas , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Prognóstico
9.
J Muscle Res Cell Motil ; 42(2): 203-217, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32990898

RESUMO

Skeletal muscle satellite cells (SCs) play an important role in the repairment and regeneration of damaged muscle. The activation, proliferation, migration, and differentiation of SCs are essential to the response to muscle injury. Up-frameshift 1 (UPF1) is involved in the regulation of many developmental processes. However, the role of UPF1 and its associated regulatory mechanism in SCs are still unclear. Here, we analyzed changes in the transcriptome of porcine SCs with UPF1 knockdown. The results showed that focal adhesion and actin cytoskeleton processes were regulated by UPF1. We also confirmed experimentally that UPF1 promoted SC migration and adhesion by regulating the expression of F-Actin, Vinculin, and several adhesion-related genes. Furthermore, we found that phosphorylated focal adhesion kinase (p-FAK) was down-regulated by UPF1 knockdown. This study identifies the role of UPF1 in regulating SC migration and adhesion and therefore provides new insight into the regulatory mechanism of UPF1 in the process of repairing damaged muscle.


Assuntos
Células Satélites de Músculo Esquelético , Actinas , Animais , Adesão Celular , Diferenciação Celular , Músculo Esquelético , RNA , Suínos
10.
Int J Mol Sci ; 22(8)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33916886

RESUMO

The lipid droplet is a kind of organelle that stores neutral lipids in cells. Recent studies have found that in addition to energy storage, lipid droplets also play an important role in biological processes such as resistance to stress, immunity, cell proliferation, apoptosis, and signal transduction. Lipid droplets are formed at the endoplasmic reticulum, and mature lipid droplets participate in various cellular processes. Lipid droplets are decomposed by lipase and lysosomes. In the life of a lipid droplet, the most important thing is to interact with other organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and autophagic lysosomes. The interaction between lipid droplets and other organelles requires them to be close to each other, which inevitably involves the motility of lipid droplets. In fact, through many microscopic observation techniques, researchers have discovered that lipid droplets are highly dynamic organelles that move quickly. This paper reviews the process of lipid droplet motility, focusing on explaining the molecular basis of lipid droplet motility, the factors that regulate lipid droplet motility, and the influence of motility on the formation and decomposition of lipid droplets. In addition, this paper also proposes several unresolved problems for lipid droplet motility. Finally, this paper makes predictions about the future research of lipid droplet motility.


Assuntos
Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos , Animais , Transporte Biológico , Humanos , Espaço Intracelular/metabolismo
11.
Opt Express ; 28(7): 9666-9676, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32225569

RESUMO

We report the generation of vortex soliton molecules (VSMs) in a passively mode-locked fiber laser based on a mode selective coupler (MSC). ±1-order VSMs with variable numbers of molecules are observed. By adjusting the polarization state of the light in the cavity, we further demonstrate the process in which one VSM splits to multiple. During this process, the number of the solitons inside the VSM also varies and their separation gradually increases while the spectral modulation being unobservable, and vice versa. The obtained results have potential applications in fields of optical communications, especially in information coding.

12.
Int J Mol Sci ; 21(21)2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33147895

RESUMO

Lipid homeostasis is essential for normal cell physiology. Generally, lipids are stored in a lipid droplet (LD), a ubiquitous organelle consisting of a neutral lipid core and a single layer of phospholipid membrane. It is thought that LDs are generated from the endoplasmic reticulum and then released into the cytosol. Recent studies indicate that LDs can exist in the nucleus, where they play an important role in the maintenance of cell phospholipid homeostasis. However, the details of nuclear lipid droplet (nLD) generation have not yet been clearly characterized. SEIPIN is a nonenzymatic protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene. It is associated with lipodystrophy diseases. Many recent studies have indicated that SEIPIN is essential for LDs generation. Here, we review much of this research in an attempt to explain the role of SEIPIN in nLD generation. From an integrative perspective, we conclude by proposing a theoretical model to explain how SEIPIN might participate in maintaining homeostasis of lipid metabolism.


Assuntos
Núcleo Celular/metabolismo , Citosol/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/genética , Homeostase , Lipídeos/química , Animais , Diferenciação Celular , Retículo Endoplasmático/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Humanos , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Fosfolipídeos/química
13.
BMC Mol Biol ; 20(1): 24, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703613

RESUMO

BACKGROUND: Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC). The lipid-rich environment enhances the proliferation and metastasis abilities of tumor cells. Previous studies showed the effect of the ubiquitin-proteasome system (UPS) on tumor cell proliferation. However, the underlying mechanism of UPS in regulating the proliferation of lipid-rich tumor cells is not totally clear. RESULTS: Here, we identify two proteasome 26S subunits, non-ATPase 1 and 2 (PSMD1 and PSMD2), which regulate HepG2 cells proliferation via modulating cellular lipid metabolism. Briefly, the knockdown of PSMD1 and/or PSMD2 decreases the formation of cellular lipid droplets, the provider of the energy and membrane components for tumor cell proliferation. Mechanically, PSMD1 and PSMD2 regulate the expression of genes related to de novo lipid synthesis via p38-JNK and AKT signaling. Moreover, the high expression of PSMD1 and PSMD2 is significantly correlated with poor prognosis of HCC. CONCLUSION: We demonstrate that PSMD1 and PSMD2 promote the proliferation of HepG2 cells via facilitating cellular lipid droplet accumulation. This study provides a potential therapeutic strategy for the treatment of lipid-rich tumors.


Assuntos
Gotículas Lipídicas/metabolismo , Complexo de Endopeptidases do Proteassoma/fisiologia , Fator 2 Associado a Receptor de TNF/fisiologia , Apoptose , Proliferação de Células , Células Hep G2 , Humanos , Metabolismo dos Lipídeos , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo
14.
Opt Express ; 27(20): 28507-28522, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684601

RESUMO

Pulsating behavior is a universal phenomenon in versatile fields. In nonlinear dissipative systems, the solitons also pulsate under proper conditions and show many interesting dynamics. However, the pulsation dynamics are generally concerned with single-soliton cases. Herein, by utilizing real-time spectroscopy technique, namely, dispersive Fourier-transform (DFT), we reveal the distinct dynamical diversity of pulsating solitons in a fiber laser. In particular, the weak to strong explosive behaviors of pulsating solitons, as well as the rogue wave generation during explosions are observed. Moreover, the concept of soliton pulsation is extended to the multi-soliton case. It is found that the simultaneous pulsations of energy, separation and relative phase difference could be observed for solitons inside the molecule, while the pulsations of each individual in a multi-soliton bunch could be regular or irregular. These findings will shed new insights into the complex nonlinear behavior of solitons in ultrafast fiber lasers as well as dissipative optical systems.

15.
Int J Mol Sci ; 19(11)2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30400205

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has become the world's most common liver disease. The disease can develop liver fibrosis or even carcinomas from the initial hepatic steatosis, and this process is influenced by many factors. Reactive oxygen species (ROS), as potent oxidants in cells, have been reported previously to play an important role in the development of NAFLD progression via promoting neutral lipid accumulation. Here, we found that ROS can promote lipid droplet formation in hepatocytes by promoting perilipin2 (PLIN2) expression. First, we used different concentrations of hydrogen peroxide to treat HepG2 cells and found that the number of lipid droplets in the cells increased, however also that this effect was dose-independent. Then, the mRNA level of several lipid droplet-associated genes was detected with hydrogen peroxide treatment and the expression of PLIN2, PLIN5, and FSP27 genes was significantly up-regulated (p < 0.05). We overexpressed PLIN2 in HepG2 cells and found that the lipid droplets in the cells were markedly increased. Interference with PLIN2 inhibits ROS-induced lipid droplet formation, revealing that PLIN2 is a critical factor in this process. We subsequently analyzed the regulatory pathway and protein interaction network that is involved in PLIN2 and found that PLIN2 can regulate intracellular lipid metabolism through the PPARα/RXRA and CREB/CREBBP signaling pathways. The majority of the data indicated the correlation between hydrogen peroxide-induced PLIN2 and lipid droplet upregulation. In conclusion, ROS up-regulates the expression of PLIN2 in hepatocytes, whereas PLIN2 promotes the formation of lipid droplets resulting in lipid accumulation in liver tissues.


Assuntos
Gotículas Lipídicas/metabolismo , Perilipina-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Proteína de Ligação a CREB/metabolismo , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Mapas de Interação de Proteínas , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos
16.
Cell Death Discov ; 9(1): 254, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474495

RESUMO

Lipid droplets (LDs) are cellular organelles comprising a core of neutral lipids (glycerides, sterols) encased within a single phospholipid membrane, responsible for storing surplus lipids and furnishing cellular energy. LDs engage in lipid synthesis, catabolism, and transport processes by interacting with other organelles (e.g., endoplasmic reticulum, mitochondria), and they play critical roles in regulating cellular stress and immunity. Recent research has uncovered that an elevated number of LDs is a hallmark of cancer cells, attributable to their enhanced lipid uptake and synthesis capacity, with lipids stored as LDs. Depletion of LDs in cancer cells induces apoptosis, prompting the emergence of small molecule antitumor drugs targeting LDs or key factors (e.g., FASN, SCD1) within the lipid synthesis pathway. Advancements in LD isolation and artificial synthesis have demonstrated their potential applicability in antitumor research. LDs extracted from murine adipose tissue and incubated with lipophilic antitumor drugs yield drug-coated LDs, which promote apoptosis in cancer cells. Furthermore, LDs have been employed as biological lenses to augment the resolution of subcellular structures (microfilaments, microtubules), facilitating the observation of intricate structures within thicker cells, including cancer cells. This review delineates the functional and metabolic mechanisms of LDs in cancer cells and encapsulates recent progress in LD-centered antitumor research, offering novel insights for tumor diagnosis and treatment.

17.
Asia Pac J Clin Oncol ; 18(5): e318-e328, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34821067

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Patients have a low survival rate and a high recurrence rate, and AML is a highly heterogeneous disease without an effective and specific targeted therapy. AIMS: Therefore, it is urgent to explore new AML markers to enable early diagnosis and find drug targets for individualized treatment. RESULTS: Herein, we demonstrate that O-linked-N-acetylglucosamine transferase (OGT) is significantly upregulated in AML tissues compared with normal tissues. The high level of OGT expression is significantly related to poor overall survival (OS) in AML. Inhibition of OGT can inhibit AML cell proliferation and promote AML cell apoptosis. CONCLUSION: These results suggest that OGT plays an important role in the pathogenesis of AML, and may become a potential biomarker and molecular drug target for precision therapy for AML.


Assuntos
Leucemia Mieloide Aguda , N-Acetilglucosaminiltransferases , Proliferação de Células , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismo , Regulação para Cima
18.
Commun Biol ; 5(1): 326, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388144

RESUMO

Hepatic steatosis is the main characteristic of some liver metabolism diseases. However, unclear molecular mechanism of hepatic steatosis impedes the therapy of this hepatic steatosis. Glutathione-S-transferase mu 2 (GSTM2), as a member of phase II drug metabolizing enzymes (DMEs), regulates cellular antioxidant and detoxificant. GSTM2 was highly up-regulated in hepatic steatosis tissues and high-fat diet (HFD) fed mice. Loss-of-function GSTM2 mouse model demonstrated that GSTM2 protected mice from excess fat accumulation. Mechanistically, GSTM2 interacted with ASK1 and suppressed its phosphorylation and the activation of subsequent downstream p38-JNK signalling. Moreover, GSTM2 overexpression in the liver effectively ameliorated hepatic lipid accumulation. Therefore, we identified GSTM2 as an important negative regulator in progression of hepatic steatosis via both its detoxification/antioxidant and inhibition of ASK1-p38/JNK signalling. This study showed potential therapeutic function of the DME in progression of hepatic steatosis.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Antioxidantes , Glutationa Transferase/genética , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo
19.
Nanomaterials (Basel) ; 12(4)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35215001

RESUMO

Lipid droplets (LDs) play an important role in the regulation of cellular stress. This suggests LDs can be applied as safe and effective biomaterials to alleviate cellular stress and lipotoxicity. Here, we constructed a convenient method to generate stable and pure artificial lipid droplets (aLDs). aLDs can maintain their biological function by incubating LD-associated proteins or organelles in vitro. It was validated that perilipin-coated aLDs could be uptaken by cells, significantly reducing hydrogen peroxide-induced reactive oxidative species (ROS) and alleviating cellular lipotoxicity caused by excess fatty acid. Our work demonstrated a direct role of LDs in regulating cellular stress levels, providing methods and potential value for future research and medical applications of LDs.

20.
Cell Death Dis ; 12(12): 1102, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815388

RESUMO

Lipid droplet (LD), a multi-functional organelle, is found in most eukaryotic cells. LDs participate in the regulation of many cellular processes including proliferation, stress, and apoptosis. Previous studies showed the athlete's paradox that trained athletes accumulate LDs in their skeletal muscle. However, the impact of LDs on skeletal muscle and myogenesis is not clear. We discovered that C2C12 myoblast cells containing more LDs formed more multinucleated muscle fibers. We also discovered that LDs promoted cell migration and fusion by promoting actin-filaments remodeling. Mechanistically, two LD-proteins, Acyl-CoA synthetase long chain family member 3 (ACSL3) and lysophosphatidylcholine acyltransferase 1 (LPCAT1), medicated the recruitment of actinin proteins which contributed to actin-filaments formation on the surface of LDs. During remodeling, the actinin proteins on LDs surface translocated to actin-filaments via ARF1/COPI vesicles. Our study demonstrate LDs contribute to cell differentiation, which lead to new insight into the LD function.


Assuntos
Gotículas Lipídicas/metabolismo , Diferenciação Celular , Humanos , Transfecção
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