Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

2010 ◽  
Vol 298 (5) ◽  
pp. G608-G614 ◽  
Author(s):  
Yukihiro Fujita ◽  
Ali Asadi ◽  
Gary K. Yang ◽  
Yin Nam Kwok ◽  
Timothy J. Kieffer
Keyword(s):  
Active Form ◽  
Biologically Active ◽  
Peptide Sequence ◽  
Acid Form ◽  
Truncated Form ◽  
Differential Processing ◽  
K Cells ◽  
Naturally Occurring ◽  
Amino Acid Form

Glucose-dependent insulinotropic polypeptide (GIP) is a hormone released from enteroendocrine K cells in response to meals. Posttranslational processing of the precursor protein pro-GIP at residue 65 by proprotein convertase subtilisin/kexin type 1 (PC1/3) in gut K cells gives rise to the established 42-amino-acid form of GIP (GIP1–42). However, the pro-GIP peptide sequence contains a consensus cleavage site for PC2 at residues 52–55 and we identified PC2 immunoreactivity in a subset of K cells, suggesting the potential existence of a COOH-terminal truncated GIP isoform, GIP1–30. Indeed a subset of mouse and human K cells display GIP immunoreactivity with GIP antibodies directed to the mid portion of the peptide, but not with a COOH-terminal-directed GIP antibody, indicative of the presence of a truncated form of GIP. This population of cells represents ∼5–15% of the total GIP-immunoreactive cells in mice, depending on the region of intestine, and is virtually absent in mice lacking PC2. Amidated GIP1–30 and GIP1–42 have comparable potency at stimulating somatostatin release in the perfused mouse stomach. Therefore, GIP1–30 represents a naturally occurring, biologically active form of GIP.

scholarly journals Angiogenic Effects of Extracellular Human Immunodeficiency Virus Type 1 Tat Protein and Its Role in the Pathogenesis of AIDS-Associated Kaposi's Sarcoma

2002 ◽  
Vol 15 (2) ◽  
pp. 310-326 ◽  
Author(s):  
Giovanni Barillari ◽  
Barbara Ensoli
Keyword(s):  
Human Immunodeficiency Virus ◽  
Kaposi's Sarcoma ◽  
Secretory Pathway ◽  
Active Form ◽  
Kaposi’S Sarcoma ◽  
Biologically Active ◽  
Viral Gene ◽  
Tat Protein ◽  
Immunodeficiency Virus

SUMMARY The Tat protein of human immunodeficiency virus (HIV) type 1 is a transactivator of viral gene expression that is required for virus replication and spread. Moreover, Tat is released by acutely HIV-infected cells via a leaderless secretory pathway and in a biologically active form that exerts effects on both HIV-infected and uninfected cells from different organs and systems. This review focuses on the activities of extracellular Tat protein on endothelial cells, on angiogenesis, and on the pathogenesis of AIDS-associated angioproliferative diseases such as Kaposi's sarcoma. In particular, we discuss results from different groups indicating that Tat mimics the proangiogenic activities of extracellular matrix molecules and that it enhances the effects of angiogenic factors.

scholarly journals Proteolytic Cleavage of Human Chromogranin A Containing Naturally Occurring Catestatin Variants: Differential Processing at Catestatin Region by Plasmin

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 749-757 ◽  
Author(s):  
Nilima Biswas ◽  
Sucheta M. Vaingankar ◽  
Manjula Mahata ◽  
Madhusudan Das ◽  
Jiaur R. Gayen ◽  
...  
Keyword(s):  
Plasma Level ◽  
Chromogranin A ◽  
Strong Association ◽  
Proteolytic Processing ◽  
Biologically Active ◽  
Wild Type ◽  
Differential Processing ◽  
Amino Acid Peptide ◽  
Naturally Occurring ◽  
Local Secondary Structure

The plasma level of chromogranin A (CgA) is elevated in genetic hypertension. Conversely, the plasma level of the CgA peptide catestatin is diminished in individuals with established hypertension and those with a genetic risk of this disease. Resequencing of the human CHGA gene identified three naturally occurring variants of catestatin (Gly364Ser, Pro370Leu, and Arg374Gln) that exhibit different potencies in inhibiting catecholamine secretion. Here, we have examined whether there is any differential processing of the three CHGA variants to catestatin by the endoproteolytic enzyme plasmin. Plasmin digestion of the purified CgA proteins generated a stable biologically active 14-amino acid peptide (human CgA360–373) from the wild-type, Gly364Ser, and Arg374Gln proteins despite the disruption of the dibasic site (Arg373Arg374) in the Arg374Gln variant. Unexpectedly, the action of plasmin in generating the catestatin peptide from the Pro370Leu protein was less efficient. The efficiency of cleavage at the dibasic Arg373↓Arg374 site in synthetic human CgA360–380 was 3- to 4-fold less in Pro370Leu CgA, compared with the wild type. Circular dichroism of the synthetic CgA352–372 suggested a difference in the amount of α-helix and β-sheet between the wild-type and Pro370Leu CgA peptides. Because the Pro370 residue is in the P4 position, the local secondary structure in the vicinity of the cleavage site may enforce the specificity or accessibility to plasmin. The less efficient proteolytic processing of the Pro370Leu protein by plasmin, coupled with the strong association of this variant with ethnicity, suggests that the Pro370Leu CHGA gene variant may contribute to the differential prevalence of cardiovascular disease across ethnic groups.

Role of type 1 and 2 deiodinases in thyroid metabolism (review)

2016 ◽  
Vol 62 (2) ◽  
pp. 46-52 ◽  
Author(s):  
Gulnora M. Artykbaeva
Keyword(s):  
Active Form ◽  
Biologically Active ◽  
Reverse T3 ◽  
Iodothyronine Deiodinases ◽  
Control Growth ◽  
Brown Adipose ◽  
Thyroid Metabolism ◽  
A Cell

Thyroid hormones control growth, development and metabolism in animals. The iodothyronine deiodinases catalyze the removal of an iodine residue from outer or inner ring of the pro-hormone thyroxin (T4) molecule, thus producing either the active form triiodothyronine (T3; activation) or inactive metabolites (reverse T3; inactivation), respectively. Type 1 deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on thyroid metabolism in physiology and pathology. Type 2 deiodinase (D2) initiates thyroid hormone signaling by activating the T4 to the biologically active T3 molecule followed by gene expression on a cell-specific basis. Expression of D2 in such specific tissues as hypothalamus, pitutary, brain, brown adipose tissue, cochlea, retina, skeleton demonstrates the role of enzyme in physiology of these organs suggesting further therapeutic application. The current review intended to provide an updated picture of the recent advances concerning the molecular properties of D1 and D2 as well as their role in physiology.

scholarly journals Immunogenicity and Protective Efficacy of Oligomeric Human Immunodeficiency Virus Type 1 gp140

2001 ◽  
Vol 75 (2) ◽  
pp. 645-653 ◽  
Author(s):  
Patricia L. Earl ◽  
Wataru Sugiura ◽  
David C. Montefiori ◽  
Christopher C. Broder ◽  
Susan A. Lee ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Protective Efficacy ◽  
Active Form ◽  
Biologically Active ◽  
Homologous Virus ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linked to the ectodomain of gp41 (P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss, J. Virol. 68:3015–3026, 1994). Here we compared the antibody responses of rabbits to gp120 and gp140 that had been produced and purified in an identical manner. The gp140 antisera exhibited enhanced cross-reactivity with heterologous Env proteins as well as greater neutralization of HIV-1 compared to the gp120 antisera. To examine both immunogenicity and protective efficacy, we immunized rhesus macaques with oligomeric gp140. Strong neutralizing antibodies against a homologous virus and modest neutralization of heterologous laboratory-adapted isolates were elicited. No neutralization of primary isolates was observed. However, a substantial fraction of the neutralizing activity could not be blocked by a V3 loop peptide. After intravenous challenge with simian-HIV virus SHIV-HXB2, three of the four vaccinated macaques exhibited no evidence of virus replication.

scholarly journals Elevated Levels of High-Molecular-Weight Adiponectin in Type 1 Diabetes

2008 ◽  
Vol 93 (8) ◽  
pp. 3186-3191 ◽  
Author(s):  
Henrik Leth ◽  
Kristian K. Andersen ◽  
Jan Frystyk ◽  
Lise Tarnow ◽  
Peter Rossing ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Type 1 Diabetes ◽  
High Molecular Weight ◽  
Active Form ◽  
Biologically Active ◽  
Diabetic Patients ◽  
High Molecular Weight Adiponectin ◽  
Total Adiponectin ◽  
Type 1 Diabetic Patients

Abstract Background: Several studies have shown that type 1 diabetic patients have elevated total levels of the adipocyte-derived adipocytokine adiponectin. However, adiponectin circulates in three different subforms, and the high-molecular-weight (HMW) subform is believed to be the primary biologically active form. The effects of the medium-molecular-weight (MMW) subform and the low-molecular-weight (LMW) subform are still unresolved. Purpose: The objective of the study was to investigate the distribution of the three molecular subforms of adiponectin in well-characterized groups of type 1 diabetics with varying degrees of nephropathy as well as in healthy control subjects. Study Population: Two hundred seven individuals were included: 58 type 1 diabetics with normoalbuminuria, 46 with microalbuminuria, 46 with macroalbuminuria, and 57 matched controls. Methods: The HMW, MMW, and LMW subforms were measured using a validated in-house time-resolved immunoflourometric assay after separation by fast protein liquid chromatography. Results: The absolute concentrations of total adiponectin and all subforms were higher in type 1 diabetic patients than healthy controls. However, the relative HMW fraction was up-regulated in type 1 diabetes (P < 0.001), whereas the MMW (P < 0.001) and LMW fractions (P < 0.05) were down-regulated, compared with controls. Accordingly, the increase in concentration of total adiponectin was primarily caused by a major increase of the HMW subform. Levels of total adiponectin and the HMW subform (absolute and relative) were generally unaffected by nephropathy status defined by urinary albumin excretion rate. Conclusion: Type 1 diabetes per se is associated with higher adiponectin levels than healthy subjects. This increase is mainly explained by an elevation in the HMW subform. The elevation is unaffected by gender and diabetic kidney disease.

Processing and Characterization of Recombinant von Willebrand Factor Expressed in Different Cell Types Using a Vaccinia Virus Vector

1992 ◽  
Vol 67 (01) ◽  
pp. 154-160 ◽  
Author(s):  
P Meulien ◽  
M Nishino ◽  
C Mazurier ◽  
K Dott ◽  
G Piétu ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Von Willebrand Factor ◽  
Human Fibroblasts ◽  
Active Form ◽  
Cell Types ◽  
Biologically Active ◽  
L Cells ◽  
Von Willebrand ◽  
Different Cell Types ◽  
Willebrand Factor

SummaryThe cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgll is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells. Forty-eight hours after infection, the quantity of vWF antigen found in the cell supernatant varied from 3 to 12 U/dl depending on the cell type. By SDS-agarose gel electrophoresis, the percentage of high molecular weight forms of vWF varied from 39 to 49% relative to normal plasma for BHK, CHO, 143B and chicken cells but was less than 10% for L cells. In all cell types, the two anodic subbands of each multimer were missing. The two cathodic subbands were easily detected only in BHK and L cells. By SDS-PAGE of reduced samples, pro-vWF was present in similar quantity to the fully processed vWF subunit in L cells, present in moderate amounts in BHK and CHO and in very low amounts in 143B and chicken cells. rvWF from all cells bound to collagen and to platelets in the presence of ristocetin, the latter showing a high correlation between binding efficiency and degree of multimerization. rvWF from all cells was also shown to bind to purified FVIII and in this case binding appeared to be independent of the degree of multimerization. We conclude that whereas vWF is naturally synthesized only by endothelial cells and megakaryocytes, it can be expressed in a biologically active form from various other cell types.

Innovative approaches to the correction of chronotrope status of pregnant and lactating women

2016 ◽  
pp. 37-40
Author(s):  
S.I. Zhuk ◽  
◽  
K.K. Bondarenko ◽  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Active Form ◽  
Biologically Active ◽  
Lactating Women ◽  
Pathological Conditions ◽  
Prevention And Treatment ◽  
The Impact ◽  
High Bioavailability ◽  
Key Words Mthfr

Most recent studies show the impact of violations in the metabolism of folate and metin period in the pathogenesis of neural tube defects (NTD) of the fetus. Metafolin has a number of advantages, which primarily includes direct intake of substances in biologically active form and the optimum effect, even in the case when the patient homozygote and/or heterozygote genotype 677С T polymorphism in MTHFR. With the aim of prevention and treatment of various pathological conditions related to folate deficiency during pregnancy, it is advisable to apply vitamin-mineral complexes, containing metafolin - active form of folate with high bioavailability. Key words: MTHFR, metafolin, folic acid, pregnancy.

A REVIEW ON RECENT ADVANCES IN CHEMISTRY, SYNTHESIS AND BIOLOGICAL APPLICATIONS OF ISATIN DERIVATIVES

2018 ◽  
pp. 16-22
Author(s):  
Shukla PK ◽  
Singh MP ◽  
Patel R
Keyword(s):  
Heterocyclic Compounds ◽  
Biologically Active ◽  
Biological Applications ◽  
Plant Origin ◽  
Recent Past ◽  
Pharmacological Activities ◽  
Naturally Occurring ◽  
Recent Advances ◽  
Biological Aspects ◽  
Isatin Derivatives

Indole and its derivatives have engaged a unique place in the chemistry of nitrogen heterocyclic compounds. The recognition of the plant growthhormone, heteroauxin, the significant amino acids, tryptamine & tryptophan and anti-inflammatory drug, indomethacine are the imperativederivatives of indole which have added stimulus to this review work. Isatin (1H-indole-2,3-dione), an indole derivative of plant origin. Althoughit is a naturally occurring compound, but was synthesized by Erdmann and Laurent in 1840 before it was found in nature. Isatin is a versatileprecursor for many biologically active molecules and its diversified nature makes it a versatile substrate for further modifications. It is concernedin many pharmacological activities like anti-malarial, antiviral, anti-allergic, antimicrobial etc; isatin and its derivatives have been also found todemonstrate promising outcomes against various cancer cell lines. This review provides a brief overview on the recent advances and futureperspectives on chemistry and biological aspects of isatin and its derivatives reported in the recent past.

Naturally Occurring Organic Acid-catalyzed Facile Diastereoselective Synthesis of Biologically Active (E)-3-(arylimino)indolin-2-one Derivatives in Water at Room Temperature

2019 ◽  
Vol 23 (16) ◽  
pp. 1778-1788 ◽  
Author(s):  
Gurpreet Kaur ◽  
Arvind Singh ◽  
Kiran Bala ◽  
Mamta Devi ◽  
Anjana Kumari ◽  
...  
Keyword(s):  
Room Temperature ◽  
Biologically Active ◽  
Environmentally Benign ◽  
Diastereoselective Synthesis ◽  
Substituted Anilines ◽  
Reaction Conditions ◽  
Naturally Occurring ◽  
Acid Catalyzed ◽  
Reaction Media ◽  
Column Chromatographic

A simple, straightforward and efficient method has been developed for the synthesis of (E)-3-(arylimino)indolin-2-one derivatives and (E)-2-((4-methoxyphenyl)imino)- acenaphthylen-1(2H)-one. The synthesis of these biologically-significant scaffolds was achieved from the reactions of various substituted anilines and isatins or acenaphthaquinone, respectively, using commercially available, environmentally benign and naturally occurring organic acids such as mandelic acid or itaconic acid as catalyst in aqueous medium at room temperature. Mild reaction conditions, energy efficiency, good to excellent yields, environmentally benign conditions, easy isolation of products, no need of column chromatographic separation and the reusability of reaction media are some of the significant features of the present protocol.

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