S-adenosylhomocysteine hydrolase regulates anterior patterning in Dugesia japonica

AbstractBackgroundBiological methylation requires S-adenosylmethionine (SAM) and participates in a range of processes from modulation of gene expression via histone modifications to neurotransmitter synthesis. An important factor in all methylation reactions is the concentration ratio of SAM to methylation byproduct S-adenosylhomocysteine (SAH). SAH hydrolase, also known as adenosylhomocysteinase, depletes SAH and thereby facilitates metabolite recycling and maintains the methylation permissive SAM/SAH ratio. While the importance of SAH hydrolase in sustaining methylation is obvious on the cellular level, the function of this metabolic process on the organismal scale is not clear.ResultsWe used planarian Dugesia japonica to investigate the role SAH hydrolase in physiological homeostasis on the body-wide scale. Remarkably, pharmacological inhibition of the SAH hydrolase results in regression of anterior tissues and is accompanied by extensive apoptosis throughout the planarian body. Moreover, exposure to the SAHH inhibitor AdOx leads to changes in brain morphology and spatial shift in the expression of Wnt-modulator Notum. Strikingly, planarians are able to overcome these destructive patterning defects through regeneration of the anterior tissues and adaptation to the used inhibitor. Transcriptome analysis indicates that resistance to the SAHH inhibitor is at least partly mediated by changes in folate cycle and lipid metabolism.ConclusionsSAH hydrolase plays a critical role in planarian homeostasis and anterior patterning potentially through modulation of Wnt signaling. Moreover, planarian adaptation to the SAHH inhibitor via metabolic reprogramming suggests potential targets for addressing methylation-related human conditions.

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Updating long-held assumptions about fat stigma: For women, body shape plays a critical role

10.31234/osf.io/b6t7a ◽

2020 ◽

Author(s):

Jaimie Krems ◽

Steven L. Neuberg

Keyword(s):

Body Shape ◽

Critical Role ◽

The Body ◽

Theoretical Assumption ◽

Obesity Stigma ◽

Obese Female ◽

Three Samples ◽

Female Bodies ◽

Different Parts ◽

Fat Stigma

Heavier bodies—particularly female bodies—are stigmatized. Such fat stigma is pervasive, painful to experience, and may even facilitate weight gain, thereby perpetuating the obesity-stigma cycle. Leveraging research on functionally distinct forms of fat (deposited on different parts of the body), we propose that body shape plays an important but largely underappreciated role in fat stigma, above and beyond fat amount. Across three samples varying in participant ethnicity (White and Black Americans) and nation (U.S., India), patterns of fat stigma reveal that, as hypothesized, participants differently stigmatized equally-overweight or -obese female targets as a function of target shape, sometimes even more strongly stigmatizing targets with less rather than more body mass. Such findings suggest value in updating our understanding of fat stigma to include body shape and in querying a predominating, but often implicit, theoretical assumption that people simply view all fat as bad (and more fat as worse).

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PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22158298 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8298

Author(s):

Hugo Christian Monroy-Ramirez ◽

Marina Galicia-Moreno ◽

Ana Sandoval-Rodriguez ◽

Alejandra Meza-Rios ◽

Arturo Santos ◽

...

Keyword(s):

Liver Diseases ◽

Metabolic Regulation ◽

Structural Changes ◽

Critical Role ◽

The Body ◽

Molecular Characteristics ◽

Signal Pathways ◽

Virus Infections ◽

Physiological Processes ◽

Hepatic Level

Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development.

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Lactate secreted by PKM2 upregulation promotes Galectin-9-mediated immunosuppression via inhibiting NF-κB pathway in HNSCC

Cell Death and Disease ◽

10.1038/s41419-021-03990-4 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Hanyue Chang ◽

Qiaoshi Xu ◽

Jiayi Li ◽

Mingyu Li ◽

Zhiyuan Zhang ◽

...

Keyword(s):

Critical Role ◽

Lactate Production ◽

Metabolic Reprogramming ◽

Migration And Invasion ◽

Histone Deacetylase 3 ◽

Proliferation And Metastasis ◽

Immunosuppressive Microenvironment ◽

Transcriptional Complex

AbstractPyruvate kinase M2 as a key rate-limiting enzyme in glycolysis, it plays a critical role in metabolic reprogramming and carcinogenesis. However, whether PKM2 can promote immunosuppressive microenvironment formation remains unknown in head and neck squamous cell carcinoma (HNSCC). PKM2 expression was detected using immunohistochemical staining. The biological functions of PKM2 were investigated in vitro and in vivo. Lactate production and the expression of Galectin-9, a critical immunosuppression molecule, were detected after PKM2 knockdown and overexpression in HNSCC cells. The mechanism of lactate regulating Galectin-9 expression through NF-κB signaling was explored in vitro. Overexpression of PKM2 correlates with poor prognosis in HNSCC patients. Silencing PKM2 markedly inhibits proliferation and metastasis capacity in vivo and in vitro, and vice versa. The glycolysis and glycolytic capacity are significantly decreased after PKM2 silencing. Lactate secretion induced by PKM2 significantly promotes migration and invasion capacity. Furthermore, a positive correlation between PKM2 and Galectin-9 expression is observed in HNSCC tissues. The induction of Galectin-9 expression by PKM2 can be affected by a lactate transporter inhibitor. Mechanically, lactate impeded the suppressive transcriptional complex formation of NF-κB and histone deacetylase 3 (HDAC3), which released the transcription of Galectin-9 mediated by NF-κB signaling. Our findings demonstrate that lactate produced by PKM2 upregulation promotes tumor progression and Galectin-9-mediated immunosuppression via NF-κB signaling inhibition in HNSCC, which bridges metabolism and immunosuppression. The novel PKM2-lactate-Galectin-9 axis might be a potential therapeutic target in HNSCC.

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Regulation of Osteoclast Differentiation and Activity by Lipid Metabolism

Cells ◽

10.3390/cells10010089 ◽

2021 ◽

Vol 10 (1) ◽

pp. 89

Author(s):

Haemin Kim ◽

Brian Oh ◽

Kyung-Hyun Park-Min

Keyword(s):

Lipid Metabolism ◽

Molecular Mechanisms ◽

Bone Cells ◽

Critical Role ◽

Osteoclast Differentiation ◽

Bone Diseases ◽

Metabolic Reprogramming ◽

Lipid Lowering ◽

Metabolic Bone Diseases ◽

Increased Risk

Bone is a dynamic tissue and is constantly being remodeled by bone cells. Metabolic reprogramming plays a critical role in the activation of these bone cells and skeletal metabolism, which fulfills the energy demand for bone remodeling. Among various metabolic pathways, the importance of lipid metabolism in bone cells has long been appreciated. More recent studies also establish the link between bone loss and lipid-altering conditions—such as atherosclerotic vascular disease, hyperlipidemia, and obesity—and uncover the detrimental effect of fat accumulation on skeletal homeostasis and increased risk of fracture. Targeting lipid metabolism with statin, a lipid-lowering drug, has been shown to improve bone density and quality in metabolic bone diseases. However, the molecular mechanisms of lipid-mediated regulation in osteoclasts are not completely understood. Thus, a better understanding of lipid metabolism in osteoclasts can be used to harness bone cell activity to treat pathological bone disorders. This review summarizes the recent developments of the contribution of lipid metabolism to the function and phenotype of osteoclasts.

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Neuronal Sodium Leak Channel Is Responsible for the Detection of Sodium in the Rat Median Preoptic Nucleus

Journal of Neurophysiology ◽

10.1152/jn.00417.2010 ◽

2011 ◽

Vol 105 (2) ◽

pp. 650-660 ◽

Cited By ~ 15

Author(s):

Christina Tremblay ◽

Emmanuelle Berret ◽

Mélaine Henry ◽

Benjamin Nehmé ◽

Louis Nadeau ◽

...

Keyword(s):

Close Contact ◽

Critical Role ◽

Reversal Potential ◽

Outward Current ◽

The Body ◽

Equilibrium Potential ◽

Preoptic Nucleus ◽

Leak Channel ◽

Median Preoptic Nucleus ◽

Electrophysiological Recordings

Sodium (Na+) ions are of primary importance for hydromineral and cardiovascular homeostasis, and the level of Na+ in the body fluid compartments [plasma and cerebrospinal fluid (CSF)] is precisely monitored in the hypothalamus. Glial cells seem to play a critical role in the mechanism of Na+ detection. However, the precise role of neurons in the detection of extracellular Na+ concentration ([Na+]out) remains unclear. Here we demonstrate that neurons of the median preoptic nucleus (MnPO), a structure in close contact with the CSF, are specific Na+ sensors. Electrophysiological recordings were performed on dissociated rat MnPO neurons under isotonic [Na+] (100 mM NaCl) with local application of hypernatriuric (150, 180 mM NaCl) or hyponatriuric (50 mM NaCl) external solution. The hyper- and hyponatriuric conditions triggered an in- and an outward current, respectively. The reversal potential of the current matched the equilibrium potential of Na+, indicating that a change in [Na+]out modified the influx of Na+ in the MnPO neurons. The conductance of the Na+ current was not affected by either the membrane potential or the [Na+]out. Moreover, the channel was highly selective for lithium over guanidinium. Together, these data identified the channel as a Na+ leak channel. A high correlation between the electrophysiological recordings and immunofluorescent labeling for the NaX channel in dissociated MnPO neurons strongly supports this channel as a candidate for the Na+ leak channel responsible for the Na+-sensing ability of rat MnPO neurons. The absence of NaX labeling and of a specific current evoked by a change in [Na+]out in mouse MnPO neurons suggests species specificity in the hypothalamus structures participating in central Na+ detection.

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Diesel Exhaust Particle Exposure Compromises Alveolar Macrophage Mitochondrial Bioenergetics

International Journal of Molecular Sciences ◽

10.3390/ijms20225598 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5598

Author(s):

Jonathan L. Gibbs ◽

Blake W. Dallon ◽

Joshua B. Lewis ◽

Chase M. Walton ◽

Juan A. Arroyo ◽

...

Keyword(s):

Mitochondrial Function ◽

Diesel Exhaust ◽

Critical Role ◽

Cell Communication ◽

Diesel Exhaust Particle ◽

Diesel Exhaust Particles ◽

The Body ◽

Whole Body ◽

H2o2 Production ◽

Pulmonary Macrophages

Diesel exhaust particles (DEPs) are known pathogenic pollutants that constitute a significant quantity of air pollution. Given the ubiquitous presence of macrophages throughout the body, including the lungs, as well as their critical role in tissue and organismal metabolic function, we sought to determine the effect of DEP exposure on macrophage mitochondrial function. Following daily DEP exposure in mice, pulmonary macrophages were isolated for mitochondrial analyses, revealing reduced respiration rates and dramatically elevated H2O2 levels. Serum ceramides and inflammatory cytokines were increased. To determine the degree to which the changes in mitochondrial function in macrophages were not dependent on any cross-cell communication, primary pulmonary murine macrophages were used to replicate the DEP exposure in a cell culture model. We observed similar changes as seen in pulmonary macrophages, namely diminished mitochondrial respiration, but increased H2O2 production. Interestingly, when treated with myriocin to inhibit ceramide biosynthesis, these DEP-induced mitochondrial changes were mitigated. Altogether, these data suggest that DEP exposure may compromise macrophage mitochondrial and whole-body function via pathologic alterations in macrophage ceramide metabolism.

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Obesity Accelerates Age-Associated Defects in Human B Cells Through a Metabolic Reprogramming Induced by the Fatty Acid Palmitate

Frontiers in Aging ◽

10.3389/fragi.2021.828697 ◽

2022 ◽

Vol 2 ◽

Author(s):

Daniela Frasca ◽

Maria Romero ◽

Denisse Garcia ◽

Alain Diaz ◽

Bonnie B. Blomberg

Keyword(s):

Fatty Acid ◽

B Cells ◽

Critical Role ◽

Metabolic Reprogramming ◽

Autoimmune Antibodies ◽

Human B Cells ◽

Initial Hypothesis ◽

First Time ◽

Culture Supernatants

We have measured the secretion of autoimmune antibodies in plasma samples and in culture supernatants of blood-derived B cells from four groups of individuals: young lean (YL), elderly lean (EL), young obese (YO) and elderly obese (EO). We found secretion comparable in YO and EL individuals, suggesting that obesity accelerates age-associated defects in circulating B cells. To define at least one possible molecular pathway involved, we used an in vitro model in which B cells from YL and EL individuals have been stimulated with the Fatty Acid (FA) palmitate, the most common saturated FA in the human body. The rationale to use palmitate is that there is a chronic increase in circulating levels of palmitate, due to increased spontaneous lipolysis occurring during aging and obesity, and this may induce autoimmune B cells. Results herein show that in vitro incubation of B cells from YL and EL individuals with the FA palmitate induces mRNA expression of T-bet, the transcription factor for autoimmune antibodies, as well as secretion of autoimmune IgG antibodies, with B cells from YL individuals looking similar to B cells from EL individuals, confirming our initial hypothesis. The generation of autoimmune B cells in the presence of the FA palmitate was found to be associated with a metabolic reprogramming of B cells from both YL and EL individuals. These results altogether show the critical role of the FA palmitate in inducing human B cell immunosenescence and show for the first time the importance of metabolic pathways in this process.

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Mitochondrial genome and its regulator TFAM modulates head and neck tumourigenesis through intracellular metabolic reprogramming and activation of oncogenic effectors

Cell Death and Disease ◽

10.1038/s41419-021-04255-w ◽

2021 ◽

Vol 12 (11) ◽

Author(s):

Yi-Ta Hsieh ◽

Hsi-Feng Tu ◽

Muh-Hwa Yang ◽

Yi-Fen Chen ◽

Xiang-Yun Lan ◽

...

Keyword(s):

Head And Neck ◽

Tongue Cancer ◽

Aerobic Glycolysis ◽

Lactate Production ◽

Cellular Level ◽

Metabolic Reprogramming ◽

Transport Chain ◽

Genetically Manipulated ◽

The Impact

AbstractMitochondrial transcriptional factor A (TFAM) acts as a key regulatory to control mitochondrial DNA (mtDNA); the impact of TFAM and mtDNA in modulating carcinogenesis is controversial. Current study aims to define TFAM mediated regulations in head and neck cancer (HNC). Multifaceted analyses in HNC cells genetically manipulated for TFAM were performed. Clinical associations of TFAM and mtDNA encoded Electron Transport Chain (ETC) genes in regulating HNC tumourigenesis were also examined in HNC specimens. At cellular level, TFAM silencing led to an enhanced cell growth, motility and chemoresistance whereas enforced TFAM expression significantly reversed these phenotypic changes. These TFAM mediated cellular changes resulted from (1) metabolic reprogramming by directing metabolism towards aerobic glycolysis, based on the detection of less respiratory capacity in accompany with greater lactate production; and/or (2) enhanced ERK1/2-Akt-mTORC-S6 signalling activity in response to TFAM induced mtDNA perturbance. Clinical impacts of TFAM and mtDNA were further defined in carcinogen-induced mouse tongue cancer and clinical human HNC tissues; as the results showed that TFAM and mtDNA expression were significantly dropped in tumour compared with their normal counterparts and negatively correlated with disease progression. Collectively, our data uncovered a tumour-suppressing role of TFAM and mtDNA in determining HNC oncogenicity and potentially paved the way for development of TFAM/mtDNA based scheme for HNC diagnosis.

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Plastid-Localized EMB2726 Is Involved in Chloroplast Biogenesis and Early Embryo Development in Arabidopsis

Frontiers in Plant Science ◽

10.3389/fpls.2021.675838 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chuanling Li ◽

Jian-Xiu Shang ◽

Chenlei Qiu ◽

Baowen Zhang ◽

Jinxue Wang ◽

...

Keyword(s):

Chloroplast Development ◽

Developmental Process ◽

Higher Plants ◽

Critical Role ◽

Elongation Factor ◽

Early Embryo ◽

The Body ◽

Insertion Mutant ◽

Cell Stage ◽

Dna Insertion

Embryogenesis is a critical developmental process that establishes the body organization of higher plants. During this process, the biogenesis of chloroplasts from proplastids is essential. A failure in chloroplast development during embryogenesis can cause morphologically abnormal embryos or embryonic lethality. In this study, we isolated a T-DNA insertion mutant of the Arabidopsis gene EMBRYO DEFECTIVE 2726 (EMB2726). Heterozygous emb2726 seedlings produced about 25% albino seeds with embryos that displayed defects at the 32-cell stage and that arrested development at the late globular stage. EMB2726 protein was localized in chloroplasts and was expressed at all stages of development, such as embryogenesis. Moreover, the two translation elongation factor Ts domains within the protein were critical for its function. Transmission electron microscopy revealed that the cells in emb2726 embryos contained undifferentiated proplastids and that the expression of plastid genome-encoded photosynthesis-related genes was dramatically reduced. Expression studies of DR5:GFP, pDRN:DRN-GFP, and pPIN1:PIN1-GFP reporter lines indicated normal auxin biosynthesis but altered polar auxin transport. The expression of pSHR:SHR-GFP and pSCR:SCR-GFP confirmed that procambium and ground tissue precursors were lacking in emb2726 embryos. The results suggest that EMB2726 plays a critical role during Arabidopsis embryogenesis by affecting chloroplast development, possibly by affecting the translation process in plastids.

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Kirlian Experimental Analysis and IoT

International Journal of Reliable and Quality E-Healthcare ◽

10.4018/ijrqeh.2021040104 ◽

2021 ◽

Vol 10 (2) ◽

pp. 29-43

Author(s):

Rohit Rastogi ◽

Mamta Saxena ◽

Devendra K. Chaturvedi ◽

Mayank Gupta ◽

Akshit Rajan Rastogi ◽

...

Keyword(s):

Nervous System ◽

Energy Levels ◽

Critical Role ◽

The Body ◽

Extensive Literature ◽

Entire Body ◽

Body Parts ◽

Sodium Potassium ◽

Charged Ions ◽

The Brain

Our entire body, including the brain and nervous system, works with the help of various kinds of biological stuff which includes positively charged ions of elements like sodium, potassium, and calcium. The different body parts have different energy levels, and by measuring the energy level, we can also measure the fitness of an individual. Moreover, this energy and fitness are directly related to mental health and the signals being transmitted between the brain and other parts of the body. Various activities like walking, talking, eating, and thinking are performed with the help of these transmission signals. Another critical role played by them is that it helps in examining the mechanisms of cells present at various places in the human body and signaling the nervous system and brain if they are properly functioning or not. This manuscript is divided into two parts where, in the first part, it provides the introduction, background, and extensive literature survey on Kirlian experiments to measure the human's organ energy.

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