scholarly journals CHLORIDE-DEPENDENT ORGANIC PHOSPHATE SENSITIVITY OF THE OXYGENATION REACTION IN CROCODILIAN HEMOGLOBINS

1994 ◽  
Vol 192 (1) ◽  
pp. 1-11 ◽  
Author(s):  
R Weber ◽  
F White
Keyword(s):  
Molecular Mechanisms ◽  
Feedback Regulation ◽  
Organic Phosphate ◽  
Alligator Mississippiensis ◽  
Phosphate Esters ◽  
Caiman Crocodilus ◽  
Allosteric Interaction ◽  
Allosteric Effector ◽  
Intensive Exercise ◽  
O2 Supply

We show that crocodilian hemoglobins (Hbs), which previously have been considered to be model pigments lacking allosteric interaction with organic phosphate esters, do exhibit oxylabile ATP and 2,3-diphosphoglycerate (DPG) binding that decreases O2 affinity and increases pH sensitivity (Bohr effect), in the absence of Cl- and at the low Cl- concentrations that may occur in crocodilian plasma during 'post-ingestive alkaline tides'. Hbs from different species vary in their phosphate sensitivities. In Alligator mississippiensis Hb, O2 affinity shows greater ATP than DPG sensitivity at low [cofactor]/[Hb] ratios. In Paleosuchus palpebrosus Hb, where even a high Cl- concentration (0.1 mol l-1) does not completely suppress the phosphate effects, the opposite is true, whereas both ATP and DPG exert similar effects in Caiman crocodilus Hb. Lactate, at concentrations that may occur after intensive exercise, similarly depresses Hb O2-affinity, indicating an O2 demand/O2 supply feedback regulation. Curiously, inositol hexaphosphate (IHP), a potent allosteric effector in other vertebrate Hbs, has no effect on A. mississippiensis and P. palpebrosus Hb and only small effects on C. crocodilus Hb, presumably because of steric hindrance at the binding site. The molecular mechanisms underlying the observations (particularly the implication of ss82-Lys, i.e. the lysine residue at position 82 of the ss-chains that binds phosphate and Cl-) are considered. Their physiological significance requires further study.

scholarly journals Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

2021 ◽  
Vol 22 (7) ◽  
pp. 3463
Author(s):  
Chia-Hung Lin ◽  
Chen-Chung Liao ◽  
Mei-Yu Chen ◽  
Teh-Ying Chou
Keyword(s):  
Molecular Mechanisms ◽  
Mrna Level ◽  
Feedback Regulation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Physiology ◽  
Hydroxyl Groups ◽  
Post Translational Modification ◽  
Translation Control ◽  
Glcnac Transferase

Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

scholarly journals Short-term regular moderate exercise improved male hypothalamic-pituitary-gonadal axis function via the reduction of hypothalamic neurokinin B expression in adult rats

2021 ◽  
Vol 25 (2) ◽  
pp. 171-177
Author(s):  
Nazli Khajehnasiri ◽  
◽  
Homayoun Khazali ◽  
Farzam Sheikhzadeh Hesari, ◽  
Hamid Reza Sadeghnia ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Serum Levels ◽  
Moderate Exercise ◽  
Short Term ◽  
Neurokinin B ◽  
Adult Rats ◽  
Hpg Axis ◽  
Intensive Exercise ◽  
Reproductive Axis ◽  
Gnrh Neurons

Introduction: In the arcuate nucleus, kisspeptin, neurokinin-B and pro-dynorphin (KNDy) neurons control the function of gonadotropin-releasing hormone (GnRH) neurons. Early investigations indicated that exercise with various intensities affects luteinizing hormone (LH) and testosterone (T) in different ways. Meanwhile the molecular mechanisms underlying its function not yet been fully understood. Accordingly, the present study evaluated the role of alterations in the levels of KNDy mRNA upstream of GnRH neurons in conveying the effects of various short-term exercise intensities on the male hypothermic-pituitary-gonadal (HPG) axis. Methods: Twenty-one adult Wistar rats were randomly divided into 3 groups: control, one-month regular moderate exercise (ME) and one-month regular intensive exercise (IE). In ME (22m/min) and IE (35m/min) groups, the rats were treated 5 days a week for 60min each day. Finally, we assessed serum levels of LH and T using the ELIZA technique and KNDy and Gnrh mRNA expression by the real-time PCR method. Results: The results revealed that in ME group the expression of Nkb was reduced and the expression of Gnrh mRNA and the LH and T serum levels were increased. However, intensive exercise did not change the serum levels of LH and T or the relative expression of kiss1, Nkb, Pdyn and Gnrh genes. Conclusion: The results suggested that monthly moderate exercise improved male reproductive axis function, while intensive exercise did not have an adverse effect on the reproductive axis. These various effects on the male HPG axis may be propagated by the change in hypothalamic Nkb gene expression.

scholarly journals SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

2018 ◽  
Vol 18 (6) ◽  
pp. 484-493 ◽  
Author(s):  
Xiang Cheng ◽  
Jianying Li ◽  
Deliang Guo
Keyword(s):  
Lipid Metabolism ◽  
Cancer Therapy ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Feedback Regulation ◽  
Negative Feedback Regulation ◽  
Expression Of Genes ◽  
New Findings

Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavageactivating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms. Recent studies have revealed that SREBPs are markedly upregulated in human cancers, providing the mechanistic link between lipid metabolism alterations and malignancies. Pharmacological or genetic inhibition of SCAP or SREBPs significantly suppresses tumor growth in various cancer models, demonstrating that SCAP/SREBPs could serve as promising metabolic targets for cancer therapy. In this review, we will summarize recent progress in our understanding of the underlying molecular mechanisms regulating SCAP/SREBPs and lipid metabolism in malignancies, discuss new findings about SREBP trafficking, which requires SCAP N-glycosylation, and introduce a newly identified microRNA-29-mediated negative feedback regulation of the SCAP/SREBP pathway. Moreover, we will review recently developed inhibitors targeting the SCAP/SREBP pathway for cancer treatment.

Diamagnetic Susceptibilities of Various Inorganic Phosphates and Organic Phosphate Esters

1993 ◽  
Vol 66 (2) ◽  
pp. 371-373 ◽  
Author(s):  
Fujio Takahashi ◽  
Yasuzo Sakai ◽  
Toshihito Yoshida
Keyword(s):  
Organic Phosphate ◽  
Phosphate Esters ◽  
Inorganic Phosphates

scholarly journals miR-181d/RBP2/NF-κB p65 Feedback Regulation Promotes Chronic Myeloid Leukemia Blast Crisis

2021 ◽  
Vol 11 ◽  
Author(s):  
Minran Zhou ◽  
Xiaolin Yin ◽  
Lixin Zheng ◽  
Yue Fu ◽  
Yue Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Blast Crisis ◽  
Leukemia Cell ◽  
Feedback Regulation ◽  
Luciferase Reporter ◽  
Western Blots

BackgroundChronic myeloid leukemia (CML) is a malignant clonal proliferative disease. Once it progresses into the phase of blast crisis (CML-BP), the curative effect is poor, and the fatality rate is extremely high. Therefore, it is urgent to explore the molecular mechanisms of blast crisis and identify new therapeutic targets.MethodsThe expression levels of miR-181d, RBP2 and NF-κB p65 were assessed in 42 newly diagnosed CML-CP patients and 15 CML-BP patients. Quantitative real-time PCR, Western blots, and cell proliferation assay were used to characterize the changes induced by overexpression or inhibition of miR-181d, RBP2 or p65. Luciferase reporter assay and ChIP assay was conducted to establish functional association between miR-181d, RBP2 and p65. Inhibition of miR-181d expression and its consequences in tumor growth was demonstrated in vivo models.ResultsWe found that miR-181d was overexpressed in CML-BP, which promoted leukemia cell proliferation. Histone demethylase RBP2 was identified as a direct target of miR-181d which downregulated RBP2 expression. Moreover, RBP2 inhibited transcriptional expression of NF-κB subunit, p65 by binding to its promoter and demethylating the tri/dimethylated H3K4 region in the p65 promoter locus. In turn, p65 directly bound to miR-181d promoter and upregulated its expression. Therefore, RBP2 inhibition resulting from miR-181d overexpression led to p65 upregulation which further forwarded miR-181d expression. This miR-181d/RBP2/p65 feedback regulation caused sustained NF-κB activation, which contributed to the development of CML-BP.ConclusionsTaken together, the miR-181d/RBP2/p65 feedback regulation promoted CML-BP and miR-181d may serve as a potential therapeutic target of CML-BP.

STUDIES ON THE PRESERVATION OF BLOOD: VII. THE INFLUENCE OF INOSINE ON THE METABOLIC BEHAVIOR OF THE ERYTHROCYTE DURING THE PRESERVATION OF BLOOD IN THE COLD

1959 ◽  
Vol 37 (1) ◽  
pp. 69-79
Author(s):  
D. Rubinstein ◽  
S. Kashket ◽  
Rhoda Blostein ◽  
O. F. Denstedt
Keyword(s):  
Cold Storage ◽  
Organic Phosphate ◽  
Phosphate Esters ◽  
Blood Samples ◽  
The Third ◽  
Duration Of Storage ◽  
The Difference ◽  
Blood Specimens ◽  
Metabolic Behavior ◽  
High Degree

Inosine, like other purine nucleosides when added to preserved blood specimens, induces a resynthesis of organic phosphate esters in the erythrocytes. Apart from the difference in rates of reaction, the metabolic reconstitution of the cells is the same at 37° and 4 °C. The reconstitution of the esters occurs rapidly even at 4 °C, and the higher the concentration of inosine added, the more prolonged is the maintenance of the esters. When inosine was added repeatedly to blood samples during storage, a phase of synthesis was induced with each addition of nucleoside. The capacity of the erythrocytes to resynthesize 2,3-diphosphoglyceric acid (DPG) remained normal regardless of the storage age of the sample but the capacity to replenish ATP decreased with the duration of storage. Addition of inosine at the end of the third week of cold storage can effect a high degree of restoration of metabolic viability in the cells at 4 °C within 24 hours.

Estrogen regulation of the molecular phenotype and active translatome of AVPV kisspeptin neurons

Endocrinology ◽  
2021 ◽  
Author(s):  
Shannon B Z Stephens ◽  
Alexander S Kauffman
Keyword(s):  
Positive Feedback ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Feedback Regulation ◽  
Rna Seq ◽  
Molecular Phenotype ◽  
Estrogen Regulation ◽  
Physiological Processes ◽  
Estrogen Effects

Abstract In females, ovarian estradiol (E2) exerts both negative and positive feedback regulation on the neural circuits governing reproductive hormone secretion, but the cellular and molecular mechanisms underlying this remain poorly understood. In rodents, ERα-expressing kisspeptin neurons in the hypothalamic anteroventral periventricular region (AVPV) are prime candidates to mediate E2 positive feedback induction of preovulatory GnRH and LH surges. E2 stimulates AVPV Kiss1 expression, but the full extent of estrogen effects in these neurons is unknown; whether E2 stimulates or inhibits other genes in AVPV Kiss1 cells has not been determined. Indeed, understanding of the function(s) of AVPV kisspeptin cells is limited, in part, by minimal knowledge of their overall molecular phenotype, as only a few genes are currently known to be co-expressed in AVPV Kiss1 cells. To provide a more detailed profiling of co-expressed genes in AVPV Kiss1 cells, including receptors and other signaling factors, and test how these genes respond to E2, we selectively isolated actively-translated mRNAs from AVPV Kiss1 cells of female mice and performed RNA-Seq. This identified >13,000 mRNAs co-expressed in AVPV Kiss1 cells, including multiple receptor and ligand transcripts positively or negatively regulated by E2. We also performed RNAscope to validate high co-expression of several transcripts identified by RNA-Seq, including Pdyn (prodynorphin), Penk (proenkephalin), Vgf (VGF), and Cartpt (CART), in female AVPV Kiss1 cells. Given the important role of AVPV kisspeptin cells in positive feedback, E2 effects on identified genes may relate to the LH surge mechanism and/or other physiological processes involving these AVPV kisspeptin cells.

Molecular aspects of the ontogeny of the pituitary-gonadal axis

1995 ◽  
Vol 7 (5) ◽  
pp. 1025 ◽  
Author(s):  
I Huhtaniemi
Keyword(s):  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Feedback Regulation ◽  
Reproductive Organs ◽  
Endocrine Function ◽  
Male Rat ◽  
Fetal Life ◽  
Hormone Production ◽  
Endocrine Activity ◽  
Hormonal Stimulus

The endocrine function of the mammalian pituitary-gonadal axis begins in utero. This is important particularly for the ontogeny and function of the male reproductive organs, the induction of which is critically dependent on the two fetal testicular hormones, testosterone and anti-mullerian hormone. In contrast, ovarian endocrine activity begins only after birth. The earliest phases of testicular hormone production are probably under autocrine or paracrine regulation, but the dependence on gonadotrophins starts in fetal life. During maturation of the hypothalamic-pituitary-testicular axis, the target organs acquire their responsiveness (viz receptors) before the onset of secretion of the tropic hormonal stimulus. The last link to develop is the feedback regulation, and the whole axis is functional in the developing male rat during the last days of gestation. Although gonadotrophin secretion starts in both sexes simultaneously, the fetal ovary is endocrinologically quiescent--its gonadotrophin responsiveness and endocrine activity begin only after birth. The fetal and postnatal periods of testicular activity have crucial effects on male sexual differentiation, whereas in the female, early sexual development occurs autonomously without influence of ovarian function. The purpose of this review is to elucidate some of the recent findings on the molecular mechanisms involved in the perinatal maturation of the rat hypothalamic-pituitary-gonadal axis.

scholarly journals Molecular mechanism for feedback regulation of C4 biosynthesis in guinea pig peritoneal macrophage.

1984 ◽  
Vol 159 (6) ◽  
pp. 1750-1761 ◽  
Author(s):  
H S Auerbach ◽  
R D Baker ◽  
W J Matthews ◽  
H R Colten
Keyword(s):  
Guinea Pig ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Plasma Concentrations ◽  
Major Histocompatibility Complex Gene ◽  
Feedback Regulation ◽  
Fluid Phase ◽  
Biologically Active ◽  
Class Iii ◽  
Factor B

Previous reports have shown that regulation of local extrahepatic production of complement may not reflect the regulation of plasma concentrations of the corresponding proteins and, further, that alteration of the tissue microenvironment can affect local macrophage protein synthesis. This report describes the molecular basis for control of the biosynthesis and secretion of a class III major histocompatibility complex gene product, the fourth component of complement (C4), from guinea pig macrophages by extracellular native C4 protein. The effect is specific for C4 synthesis, since production of C2 and total secreted protein was unaffected by fluid phase C4. C4 synthesis by extracellular C4 is regulated at a pretranslational level, without an effect on posttranslational proteolytic cleavage, glycosylation, or secretion. Specific C4 and factor B cDNA probes were used to demonstrate, by dot hybridization and Northern blot analysis, a decrease in messenger RNA coding for C4 that paralleled the inhibition of C4 biosynthesis, while the amount of total RNA and mRNA specific for factor B remained constant. Inhibition of C4 biosynthesis and the disappearance of mRNA encoding C4 occurred between 4 and 6 h after exposure of the macrophages to biologically active or methylamine-inactivated C4 protein. These data demonstrate that regulation of C4 biosynthesis by guinea pig macrophages serves as a model for the study of the molecular mechanisms of macrophage activation as well as the control of production of a component of the inflammatory response.

Growth rates of black caiman (Melanosuchus niger) and spectacled caiman (Caiman crocodilus) from two different Amazonian flooded habitats

2013 ◽  
Vol 34 (4) ◽  
pp. 437-449 ◽  
Author(s):  
Ronis Da Silveira ◽  
Zilca Campos ◽  
John Thorbjarnarson ◽  
William E. Magnusson
Keyword(s):  
Growth Rates ◽  
Biotic Interactions ◽  
Alligator Mississippiensis ◽  
Growth And Survival ◽  
Density Dependent ◽  
Demographic Models ◽  
Caiman Crocodilus ◽  
Dependent Growth ◽  
Rates Of Growth ◽  
Dependent Processes

Rates of growth and survival in wild populations are affected by the physical environment, biotic interactions, and density-dependent processes, such as growth and fecundity. However, the relative importance of these factors in long-lived reptiles is poorly understood. We analyzed growth rates of Melanosuchus niger and Caiman crocodilus coexisting in two areas of the Brazilian Amazon with very different environmental characteristics. Growth rates of Caiman crocodilus at the two sites were similar, but M. niger grew more slowly in the area with higher productivity and higher density of caimans. Growth rates of the same species from other sites and of the temperate-zone Alligator mississippiensis indicate large differences among sites, but little evidence that these differences are primarily due to differences in productivity or temperature. Demographic models used to estimate sustained yields from caiman harvests should take into account the likely importance of density-dependent growth.

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