Different Biological Effects of Unmodified Prolactin and a Molecular Mimic of Phosphorylated Prolactin Involve Different Signaling Pathways†

In mammals, Myostatin (MSTN) is a known negative regulator of muscle growth and development, but its role in birds is poorly understood. To investigate the molecular mechanism of MSTN on muscle growth and development in chickens, we knocked out MSTN in chicken fetal myoblasts (CFMs) and sequenced the mRNA transcriptomes. The amplicon sequencing results show that the editing efficiency of the cells was 76%. The transcriptomic results showed that 296 differentially expressed genes were generated after down-regulation of MSTN, including angiotensin I converting enzyme (ACE), extracellular fatty acid-binding protein (EXFABP) and troponin T1, slow skeletal type (TNNT1). These genes are closely associated with myoblast differentiation, muscle growth and energy metabolism. Subsequent enrichment analysis showed that DEGs of CFMs were related to MAPK, P13K/AKT, and STAT3 signaling pathways. The MAPK and P13K/AKT signaling pathways are two of the three known signaling pathways involved in the biological effects of MSTN in mammals, and the STAT3 pathway is also significantly enriched in MSTN knock out chicken leg muscles. The results of this study will help to understand the possible molecular mechanism of MSTN regulating the early differentiation of CFMs and lay a foundation for further research on the molecular mechanism of MSTN involvement in muscle growth and development.

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Biological Effects of Gyrophoric Acid and Other Lichen Derived Metabolites, on Cell Proliferation, Apoptosis and Cell Signaling pathways

Chemico-Biological Interactions ◽

10.1016/j.cbi.2021.109768 ◽

2022 ◽

Vol 351 ◽

pp. 109768

Author(s):

Mahshid Mohammadi ◽

Leila Bagheri ◽

Amr Badreldin ◽

Pedram Fatehi ◽

Leila Pakzad ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Signaling ◽

Signaling Pathways ◽

Biological Effects ◽

Cell Signaling Pathways ◽

Gyrophoric Acid

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Positive Crosstalk Between Hedgehog and NF-κB Pathways Is Dependent on KRAS Mutation in Pancreatic Ductal Adenocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.652283 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yuqiong Wang ◽

Dan Wang ◽

Yanmiao Dai ◽

Xiangyu Kong ◽

Xian Zhu ◽

...

Keyword(s):

Tumor Growth ◽

Pancreatic Ductal Adenocarcinoma ◽

Signaling Pathways ◽

Kras Mutation ◽

Biological Effects ◽

Ductal Adenocarcinoma ◽

Luciferase Reporter ◽

Hh Signaling

It has been shown that aberrant activation of the Hedgehog (Hh) and nuclear factor-kappa B (NF-κB) signaling pathways plays an important role in the pancreatic carcinogenesis, and KRAS mutation is a hallmark of pancreatic ductal adenocarcinoma (PDAC). Until now, the role of KRAS mutation in the context of crosstalk between Hh and NF-κB signaling pathways in PDAC has not been investigated. This study was to determine whether the crosstalk between the Hh and NF-κB pathways is dependent on KRAS mutation in PDAC. The correlation between Gli1, Shh, NF-κB p65 expression and KRAS mutation in PDAC tissues was firstly examined by immunohistochemistry. Next, Western blotting, qPCR, and immunofluorescence were conducted to examine the biological effects of interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) as NF-κB signaling agonists, Shh as an Hh ligand alone or in combination with KRAS small interfering RNA (si-KRAS) in KRAS-mutant PDAC cells (MT-KRAS; SW1990 and Panc-1), wild-type KRAS PDAC cells (WT-KRAS; BxPC-3) and mutant KRAS knock-in BxPC-3 cells in vitro as well as tumor growth in vivo. KRAS mutation-dependent crosstalk between Hh and NF-κB in PDAC cells was further assessed by Ras activity and luciferase reporter assays. The aberrant Hh and NF-κB pathway activation was found in PDAC tissues with KRAS mutation. The same findings were confirmed in MT-KRAS PDAC cells and MT-KRAS knock-in BxPC-3 cells, whereas this activation was not observed in WT-KRAS PDAC cells. However, the activation was significantly down-regulated by KRAS silencing in MT-KRAS PDAC cells. Furthermore, MT-KRAS cancer cell proliferation and survival in vitro and tumor growth after inoculation with MT-KRAS cells in vivo were promoted by NF-κB and Hh signaling activation. The pivotal factor for co-activation of NF-κB and Hh signaling is MT-KRAS protein upregulation, showing that positive crosstalk between Hh and NF-κB pathways is dependent upon KRAS mutation in PDAC.

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The effects of 50 Hz magnetic field–exposed cell culture medium on cellular functions in FL cells

Journal of Radiation Research ◽

10.1093/jrr/rrz020 ◽

2019 ◽

Vol 60 (4) ◽

pp. 424-431 ◽

Cited By ~ 4

Author(s):

Yue Fei ◽

Liling Su ◽

Haifeng Lou ◽

Chuning Zhao ◽

Yiqin Wang ◽

...

Keyword(s):

Cell Viability ◽

Signaling Pathways ◽

Relative Permittivity ◽

Culture Medium ◽

Biological Effects ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Cell Counting ◽

International Agency ◽

Dependent Manner

Abstract Although extremely low frequency magnetic fields (ELF-MFs) have been classified as a possible carcinogen for humans by the International Agency for Research on Cancer (IARC), their biological effects and underlying mechanisms are still unclear. Our previous study indicated that ELF-MF exposure influenced the relative permittivity of the saline solution, suggesting that the MF exposure altered physical properties of the solution. To explore the biophysical mechanism of ELF-MF–induced biological effects, this study examined the effects of 50 Hz sinusoidal MF at 0–4.0 mT on the permittivity of culture medium with phase-interrogation surface plasmon resonance (SPR) sensing. Then, the biological effects of MF pre-exposed culture medium on cell viability, the mitogen-activated protein kinase (MAPK) signaling pathways, oxidative stress, and genetic stabilities were analyzed using Cell Counting Kit-8, western blot, flow cytometry, γH2AX foci formation, and comet assay. The results showed that SPR signals were decreased under MF exposure in a time- and dose-dependent manner, and the decreased SPR signals were reversible when the exposure was drawn off. However, MF pre-exposed culture medium did not significantly change cell viability, intracellular reactive oxygen species level, activation of the MARK signaling pathways, or genetic stabilities in human amniotic epithelial cells (FL cells). In conclusion, our data suggest that the relative permittivity of culture medium was influenced by 50 Hz MF exposure, but this change did not affect the biological processes in FL cells.

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Interaction between Bacillus cereus and Cultured Human Enterocytes: Effect of Calcium, Cell Differentiation, and Bacterial Extracellular Factors

Journal of Food Protection ◽

10.4315/0362-028x.jfp-12-294 ◽

2013 ◽

Vol 76 (5) ◽

pp. 820-826 ◽

Cited By ~ 8

Author(s):

JESSICA MINNAARD ◽

IVANNA S. ROLNY ◽

PABLO F. PÉREZ

Keyword(s):

Cell Differentiation ◽

Bacillus Cereus ◽

Signaling Pathways ◽

Biological Effects ◽

Eukaryotic Cells ◽

Calcium Depletion ◽

Cytoskeleton Disruption

Bacillus cereus interaction with cultured human enterocytes and the signaling pathways responsible for the biological effects of the infection were investigated. Results demonstrate that calcium depletion increases the ability of strains T1 and 2 to invade cells. Bacteria associated in greater extent to undifferentiated enterocytes and extracellular factors from strain 2 increased its own association and invasion. Inhibitors of signaling pathways related to phosphorylated lipids (U73122 and wortmannin) were able to significantly reduce cytoskeleton disruption induced by B. cereus infection. Adhesion of strain T1 decreased in the presence of U73122 and of wortmannin, as well as when those inhibitors were used together. In contrast, invasion values were diminished only by U73122. Results show that different factors are involved in the interaction between B. cereus and cultured human enterocytes. Following infection, disruption of the cytoskeleton could facilitate invasion of the eukaryotic cells.

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Dissociation between Insulin-Mediated Signaling Pathways and Biological Effects in Placental Cells: Role of Protein Kinase B and MAPK Phosphorylation

Endocrinology ◽

10.1210/endo.142.9.8391 ◽

2001 ◽

Vol 142 (9) ◽

pp. 3974-3979 ◽

Cited By ~ 11

Author(s):

Pascal Boileau ◽

Michèle Caüzac ◽

Marie Ange Pereira ◽

Jean Girard ◽

Sylvie Hauguel-de Mouzon

Keyword(s):

Protein Kinase ◽

Signaling Pathways ◽

Protein Kinase B ◽

Biological Effects ◽

Mapk Phosphorylation ◽

Placental Cells

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A review on alcohol: from the central action mechanism to chemical dependency

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.61.04.381 ◽

2015 ◽

Vol 61 (4) ◽

pp. 381-387 ◽

Cited By ~ 17

Author(s):

João Victor Vezali Costardi ◽

Rafael Augusto Teruaki Nampo ◽

Gabriella Lourenço Silva ◽

Maria Aparecida Ferreira Ribeiro ◽

Heryck José Stella ◽

...

Keyword(s):

Signaling Pathways ◽

Biological Effects ◽

Information Storage ◽

General Effect ◽

Central Action ◽

Gamma Aminobutyric Acid ◽

Action Mechanism ◽

System A ◽

The Central Nervous System ◽

Opioid Systems

SummaryIntroduction:alcohol is a psychotropic depressant of the central nervous system (CNS) that promotes simultaneous changes in several neuronal pathways, exerting a profound neurological impact that leads to various behavioral and biological alterations.Objectives:to describe the effects of alcohol on the CNS, identifying the signaling pathways that are modified and the biological effects resulting from its consumption.Methods:a literature review was conducted and articles published in different languages over the last 15 years were retrieved.Results:the studies reviewed describe the direct effect of alcohol on several neurotransmitter receptors (gamma-aminobutyric acid [GABA], glutamate, endocannabinoids AEA and 2-AG, among others), the indirect effect of alcohol on the limbic and opioid systems, and the effect on calcium and potassium channels and on proteins regulated by GABA in the hippocampus.Discussion and conclusion:the multiple actions of alcohol on the CNS result in a general effect of psychomotor depression, difficulties in information storage and logical reasoning and motor incoordination, in addition to stimulating the reward system, a fact that may explain the development of addiction. Knowledge on the neuronal signaling pathways that are altered by alcohol allows the identification of effectors which could reduce its central action, thus, offering new therapeutic perspectives for the rehabilitation of alcohol addicts.

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Nicorandil Inhibits Osteoclast Formation Base on NF-κB and p-38 MAPK Signaling Pathways and Relieves Ovariectomy-Induced Bone Loss

Frontiers in Pharmacology ◽

10.3389/fphar.2021.726361 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shenggui Xu ◽

Xiankun Cao ◽

Zhenxing Yu ◽

Wenxin He ◽

Yichuan Pang ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Signaling Pathways ◽

P38 Mapk ◽

Biological Effects ◽

Mapk Signaling ◽

Osteoclast Formation ◽

Mineral Density ◽

Mapk Activation ◽

Bone Disorders

Osteolytic bone disorders are characterized by an overall reduction in bone mineral density which enhances bone ductility and vulnerability to fractures. This disorder is primarily associated with superabundant osteoclast formation and bone resorption activity. Nicorandil (NIC) is a vasodilatory anti-anginal drug with ATP-dependent potassium (KATP) channel openings. However, NIC is adopted to manage adverse cardiovascular and coronary events. Recent research has demonstrated that NIC also possesses anti-inflammatory peculiarity through the regulation of p38 MAPK and NF-κB signaling pathways. Both MAPK and NF-κB signaling pathways play pivotal roles in RANKL-induced osteoclast formation and bone resorption function. Herein, we hypothesized that NIC may exert potential biological effects against osteoclasts, and revealed that NIC dose-dependently suppressed bone marrow macrophage (BMM) precursors to differentiate into TRAP + multinucleated osteoclasts in vitro. Furthermore, osteoclast resorption assays demonstrated anti-resorptive effects exhibited by NIC. NIC had no impact on osteoblast differentiation or mineralization function. Based on Biochemical analyses, NIC relieved RANKL-induced ERK, NF-κB and p38 MAPK signaling without noticeable effects on JNK MAPK activation. However, the attenuation of NF-κB and p38 MAPK activation was sufficient to hamper the downstream induction of c-Fos and NFATc1 expression. Meanwhile, NIC administration markedly protected mice from ovariectomy (OVX)-induced bone loss through in vivo inhibition of osteoclast formation and bone resorption activity. Collectively, this work demonstrated the potential of NIC in the management of osteolytic bone disorders mediated by osteoclasts.

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Minocycline attenuates nitric oxide-mediated neuronal and axonal destruction in vitro

Neuron Glia Biology ◽

10.1017/s1740925x05000104 ◽

2004 ◽

Vol 1 (3) ◽

pp. 297-305 ◽

Cited By ~ 20

Author(s):

ALASTAIR WILKINS ◽

MARIA NIKODEMOVA ◽

ALASTAIR COMPSTON ◽

IAN DUNCAN

Keyword(s):

Nitric Oxide ◽

Map Kinase ◽

Signaling Pathways ◽

Neuronal Death ◽

Intracellular Signaling ◽

Neuronal Survival ◽

Biological Effects ◽

Neuronal Cultures ◽

No Donor ◽

Anti Inflammatory

Minocycline, a tetracycline derivative with pleiotropic biological effects, exhibits anti-inflammatory properties in several models of CNS disease. In addition to reducing production of inflammatory mediators, it has been postulated that minocycline might also be directly neuroprotective under these circumstances. Therefore, we investigated the effect of minocycline on primary cortical neuronal cultures exposed to a nitric oxide (NO)-donor. Cultures were assessed for neuronal survival, axon survival and markers of intracellular signaling pathways. The NO donor significantly increased neuronal death and minocycline was protective under these conditions. Furthermore NO-induced reductions in axonal length were significantly attenuated by minocycline. Improvements in axonal length were dependent on mitogen-activated protein kinase (MAP kinase)/extracellular signal-related kinase (Erk) signaling, whereas phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signaling was important in neuronal survival. Further investigation into MAP kinase signaling pathways revealed inhibition of p38 MAP kinase and c-jun N-terminal kinase (JNK) signaling by minocycline. JNK pathways were activated by trophic factor-withdrawal and minocycline attenuated neuronal death induced by trophic withdrawal. These results indicate that, in addition to anti-inflammatory properties, minocycline has direct protective effects on neurons and provides further evidence for its use in disorders of the CNS.

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Sphingomyelinases and Liver Diseases

Biomolecules ◽

10.3390/biom10111497 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1497

Author(s):

Naroa Insausti-Urkia ◽

Estel Solsona-Vilarrasa ◽

Carmen Garcia-Ruiz ◽

Jose C. Fernandez-Checa

Keyword(s):

Signaling Pathways ◽

Liver Diseases ◽

De Novo ◽

Biological Effects ◽

Acyl Chain ◽

Chemical Properties ◽

Fatty Acyl ◽

Fatty Acyl Chain ◽

De Novo Synthesis ◽

Novel Treatments

Sphingolipids (SLs) are critical components of membrane bilayers that play a crucial role in their physico-chemical properties. Ceramide is the prototype and most studied SL due to its role as a second messenger in the regulation of multiple signaling pathways and cellular processes. Ceramide is a heterogeneous lipid entity determined by the length of the fatty acyl chain linked to its carbon backbone sphingosine, which can be generated either by de novo synthesis from serine and palmitoyl-CoA in the endoplasmic reticulum or via sphingomyelin (SM) hydrolysis by sphingomyelinases (SMases). Unlike de novo synthesis, SMase-induced SM hydrolysis represents a rapid and transient mechanism of ceramide generation in specific intracellular sites that accounts for the diverse biological effects of ceramide. Several SMases have been described at the molecular level, which exhibit different pH requirements for activity: neutral, acid or alkaline. Among the SMases, the neutral (NSMase) and acid (ASMase) are the best characterized for their contribution to signaling pathways and role in diverse pathologies, including liver diseases. As part of a Special Issue (Phospholipases: From Structure to Biological Function), the present invited review summarizes the physiological functions of NSMase and ASMase and their role in chronic and metabolic liver diseases, of which the most relevant is nonalcoholic steatohepatitis and its progression to hepatocellular carcinoma, due to the association with the obesity and type 2 diabetes epidemic. A better understanding of the regulation and role of SMases in liver pathology may offer the opportunity for novel treatments of liver diseases.

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