The function of glycosyl phosphoinositides in hormone action

1988 ◽  
Vol 320 (1199) ◽  
pp. 345-358 ◽  
Keyword(s):  
Membrane Fraction ◽  
Inositol Phosphate ◽  
Second Messengers ◽  
Chemical Substance ◽  
Hormone Action ◽  
Glycosyl Phosphatidylinositol ◽  
Molecular Events ◽  
Fat Liver ◽  
Hydrolysis Of

The molecular events involved in the cellular actions of insulin remain unexplained. Some of the acute actions of the hormone may be due to the intracellular generation of a chemical substance which modulates certain enzyme activities. Such an enzymemodulating substance has been identified as an inositol phosphate-glycan, produced by the insulin-sensitive hydrolysis of a glycosyl-phosphatidylinositol (glycosyl-Ptdlns) precursor. This precursor glycolipid is structurally similar to the glycosylphosphoinositide membrane protein anchor. The exposure of fat, liver or muscle cells to insulin results in the hydrolysis of glycosyl-Ptdlns, giving rise to the inositol phosphate glycan and diacylglycerol. This hydrolysis reaction is catalysed by a glycosyl-PtdIns-specific phospholipase C. This enzyme has been characterized and purified from a plasma membrane fraction of liver. This reaction also results in the acute release of certain glycosyl-Ptdlns-anchored proteins from the cell surface. Elucidation of the functional role of glycosyl-phosphoinositides in the generation of second messengers or the release of proteins may provide further insights into the pleiotropic nature of insulin action.

scholarly journals Enzymic hydrolysis of acetylcarnitine in liver from rats, sheep and cows

1975 ◽  
Vol 152 (2) ◽  
pp. 161-166 ◽  
Author(s):  
N. D. Costa ◽  
A. M. Snoswell
Keyword(s):  
Membrane Fraction ◽  
Mitochondrial Membrane ◽  
Physiological Role ◽  
Outer Mitochondrial Membrane ◽  
Carnitine Acetyltransferase ◽  
Enzymic Hydrolysis ◽  
Liver Homogenates ◽  
Hydrolysis Of ◽  
Hydrolysis Activity

1. The enzymic utilization of O-acetyl-l-carnitine other than via carnitine acetyltransferase (EC 2.3.1.7) was investigated in liver homogenates from rats, sheep and dry cows. 2. An enzymic utilization of O-acetyl-l-carnitine via hydrolysis of the ester bond to yield stoicheiometric quantities of acetate and l-carnitine was demonstrated; 0.55, 0.53 and 0.30μmol of acetyl-l-carnitine were utilized/min per g fresh wt. of liver homogenates from rats, sheep and dry cows respectively. 3. The acetylcarnitine hydrolysis activity was not due to a non-specific esterase or non-specific cholinesterase. O-Acetyl-d-carnitine was not utilized. 4. The activity was associated with the enriched outer mitochondrial membrane fraction from rat liver. Isolation of this fraction resulted in an eightfold purification of acetylcarnitine hydrolase activity. 4. The Km for this acetylcarnitine utilization was 2mm and 1.5mm for rat and sheep liver homogenates respectively. 6. There was a significant increase in acetylcarnitine hydrolase in rats on starvation and cows on lactation and a significant decrease in sheep that were severely alloxan-diabetic. 7. The physiological role of an acetylcarnitine hydrolase is discussed in relation to coupling with carnitine acetyltransferase for the relief of ‘acetyl pressure’.

scholarly journals Estrogen action on the prostate gland: a critical mix of endocrine and paracrine signaling

2007 ◽  
Vol 39 (3) ◽  
pp. 183-188 ◽  
Author(s):  
Gail P Risbridger ◽  
Stuart J Ellem ◽  
Stephen J McPherson
Keyword(s):  
Prostate Gland ◽  
Hormone Action ◽  
Autocrine Signaling ◽  
Paracrine Signaling ◽  
Estrogen Action ◽  
Signaling Mechanisms ◽  
Molecular Events ◽  
Modern Biotechnology ◽  
New Strategies

Although modern biotechnology has provided us with a greater understanding of the molecular events in endocrine-related diseases, such as benign prostatic hyperplasia and prostate cancer, these conditions continue to be a significant healthcare problem world-wide. As the number of men afflicted by these diseases will only continue to grow with the aging population, finding new strategies and new therapeutic options for the treatment of both of these diseases is crucial. A better knowledge of the mechanisms of hormone action is pivotal to making progress in the development of new hormone-based therapies. This is fundamental to increasing our understanding of the endocrine, paracrine, and autocrine signaling mechanisms in the prostate and in prostate disease, distinguishing the effects and role of each, and identifying where and how this communication goes wrong.

scholarly journals Plant inositol-phosphate-glycans and fucosylated xyloglucan oligosaccharide are accumulated upon Arabidopsis thaliana/ Botrytis cinerea infection

2021 ◽  
Author(s):  
Aline Voxeur ◽  
Julien Sechet ◽  
Samantha Vernhettes
Keyword(s):  
Arabidopsis Thaliana ◽  
Botrytis Cinerea ◽  
Inositol Phosphate ◽  
Glucose Levels ◽  
Culture Cells ◽  
Blood Glucose Levels ◽  
Molecular Pattern ◽  
Inositol Phosphate Glycans ◽  
Hydrolysis Of

In mammals, insulin is involved in controlling blood glucose levels and its role in modulating immunity is being more and more documented. This hormone promotes the release of inositolphosphate glycans (IPG) which act as mediators. In plants, one IG has already been identified in plant culture cells (Smith and Fry, 1999; Smith et al., 1999) but, to our knowledge, no IPG have been yet identified. Here, we discovered 7 IPG that are accumulated upon Arabidopsis thaliana-Botrytis cinerea interaction, concomitantly with oligogalacturonides and a fucosylated xyloglucan oligosaccharide. Further structural characterization showed that they come from the hydrolysis of polar heads of Serie A to H glycosyl inositol phosphoryl ceramides presumably via a phospholipase C activity. Taken together with the emerging role of insulin as immune regulator, these results question the role of IPG as damage associated molecular pattern both in animal and plant kingdoms.

Insulin does not induce the hydrolysis of a glycosyl phosphatidylinositol in rat fetal hepatocytes

Diabetes ◽  
1993 ◽  
Vol 42 (9) ◽  
pp. 1262-1272 ◽  
Author(s):  
J. M. Ruiz-Albusac ◽  
J. A. Zueco ◽  
E. Velazquez ◽  
E. Blazquez
Keyword(s):  
Glycosyl Phosphatidylinositol ◽  
Fetal Hepatocytes ◽  
Hydrolysis Of

scholarly journals Ca2+ Microdomains, Calcineurin and the Regulation of Gene Transcription

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Gerald Thiel ◽  
Tobias Schmidt ◽  
Oliver G. Rössler
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Gene Transcription ◽  
Intracellular Signaling ◽  
Second Messengers ◽  
Major Function ◽  
Surface Receptors ◽  
Dependent Protein

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression.

scholarly journals Steroid Sulphatase and Its Inhibitors: Past, Present and Future

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2852
Author(s):  
Paul A. Foster
Keyword(s):  
Good Evidence ◽  
The Past ◽  
Steroid Sulphatase ◽  
University Of Oxford ◽  
Therapeutic Value ◽  
Breast And Prostate Cancer ◽  
The University ◽  
Further Development ◽  
Hydrolysis Of

Steroid sulphatase (STS), involved in the hydrolysis of steroid sulphates, plays an important role in the formation of both active oestrogens and androgens. Since these steroids significantly impact the proliferation of both oestrogen- and androgen-dependent cancers, many research groups over the past 30 years have designed and developed STS inhibitors. One of the main contributors to this field has been Prof. Barry Potter, previously at the University of Bath and now at the University of Oxford. Upon Prof. Potter’s imminent retirement, this review takes a look back at the work on STS inhibitors and their contribution to our understanding of sulphate biology and as potential therapeutic agents in hormone-dependent disease. A number of potent STS inhibitors have now been developed, one of which, Irosustat (STX64, 667Coumate, BN83495), remains the only one to have completed phase I/II clinical trials against numerous indications (breast, prostate, endometrial). These studies have provided new insights into the origins of androgens and oestrogens in women and men. In addition to the therapeutic role of STS inhibition in breast and prostate cancer, there is now good evidence to suggest they may also provide benefits in patients with colorectal and ovarian cancer, and in treating endometriosis. To explore the potential of STS inhibitors further, a number of second- and third-generation inhibitors have been developed, together with single molecules that possess aromatase–STS inhibitory properties. The further development of potent STS inhibitors will allow their potential therapeutic value to be explored in a variety of hormone-dependent cancers and possibly other non-oncological conditions.

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