Tunicamycin inhibition of polyisoprenyl N-acetylglucosaminyl pyrophosphate formation in calf-liver microsomes

Tkacz, Jan S.; Lampen, J. O.

doi:10.1016/s0006-291x(75)80086-6

Cited by 844 publications

(278 citation statements)

References 17 publications

Supporting

Mentioning

271

Contrasting

Order By: Relevance

“…We next decided to take a pharmacological approach by treating HEK cells with tunicamycin, an agent that blocks protein glycosylation (Tkacz & Lampen, 1975). Fortunately, in the presence of tunicamycin, although reduced, su cient PAR 2 was expressed at the cell surface, as indicated by the calcium signal response to trypsin and the PAR 2 -AP, SLIGRL-NH 2 .…”

Section: Discussionmentioning

confidence: 99%

“…To provide further evidence that glycosylation may play a role in regulating tryptase activation of PAR 2 , we incubated HEK cells with tunicamycin (which inhibits the N-linked glycosylation of proteins (Tkacz & Lampen, 1975)) for 48 h before investigating the ability of tryptase to activate PAR 2 in the calcium signalling assay. Results are shown in Figure 3.…”

Section: Inhibition Of the Glycosylation Process By Tunicamycin Enhanmentioning

confidence: 99%

See 1 more Smart Citation

Glycosylation and the activation of proteinase‐activated receptor 2 (PAR₂) by human mast cell tryptase

Compton

Renaux

Wijesuriya

et al. 2001

British J Pharmacology

108

119

View full text Add to dashboard Cite

1 Human mast cell tryptase appears to display considerable variation in activating proteinaseactivated receptor 2 (PAR 2 ). We found tryptase to be an ine cient activator of wild-type rat-PAR 2 (wt-rPAR 2 ) and therefore decided to explore the factors that may in¯uence tryptase activation of PAR 2 . 2 Using a 20 mer peptide (P20) corresponding to the cleavage/activation sequence of wt-rPAR 2 , tryptase was as e cient as trypsin in releasing the receptor-activating sequence (SLIGRL...). However, in the presence of either human-PAR 2 or wt-r PAR 2 expressing cells, tryptase could only activate PAR 2 by releasing SLIGRL from the P20 peptide, suggesting that PAR 2 expressed on the cells was protected from tryptase activation. 3 Three approaches were employed to test the hypothesis that PAR 2 receptor glycosylation restricts tryptase activation. (a) pretreatment of wt-rPAR 2 expressing cells or human embryonic kidney cells (HEK293) with vibrio cholerae neuraminidase to remove oligosaccharide sialic acid, unmasked tryptase-mediated PAR 2 activation. (b) Inhibiting receptor glycosylation in HEK293 cells with tunicamycin enabled tryptase-mediated PAR 2 activation. (c) Wt-rPAR 2 devoid of the Nterminal glycosylation sequon (PAR 2 T25 7 ), but not rPAR 2 devoid of the glycosylation sequon located on extracellular loop-2 (PAR 2 T224A), was selectively and substantially (430 fold) more sensitive to tryptase compared with the wt-rPAR 2 . 4 Immunocytochemistry using antisera that speci®cally recognized the N-terminal precleavage sequence of PAR 2 demonstrated that tryptase released the precleavage domain from PAR 2 T25 7 but not from wt-rPAR 2 . 5 Heparin : tryptase molar ratios of greater than 2 : 1 abrogated tryptase activation of PAR 2 T25 7 . 6 Our results indicate that glycosylation of PAR 2 and heparin-inhibition of PAR 2 activation by tryptase could provide novel mechanisms for regulating receptor activation by tryptase and possibly other proteases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Inhibition Of the Glycosylation Process By Tunicamycin Enhanmentioning

confidence: 99%

Glycosylation and the activation of proteinase‐activated receptor 2 (PAR₂) by human mast cell tryptase

Compton

Renaux

Wijesuriya

et al. 2001

British J Pharmacology

108

119

View full text Add to dashboard Cite

show abstract

“…Early investigations have demonstrated that this antibiotic was able to inhibit the synthesis of N‐glycoproteins in yeast and bacteria (Kuo and Lampen 1974; Bettinger and Young 1975) as well as in animals and plants (Fig. 2) (Takatsuki and Tamura 1971; Tkacz and Lampen 1975; Ericson et al. 1977).…”

Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

194

161

View full text Add to dashboard Cite

Drug‐induced toxicity is a key issue for public health because some side effects can be severe and life‐threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug‐induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug‐induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug‐induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.

show abstract

“…TP receptors from a number of species contain two highly conserved N-linked glycosylation sites at Asn 4 and Asn 16 within their amino terminal domain (4,5, 19 -21). Impairment of N-linked glycosylation of the human TPα isoform, either through treatment with the antibiotic tunicamycin (22,23) or through site-directed mutagenesis, resulted in significantly reduced ligand binding, G protein coupling and intracellular signalling (24,25). However, these latter studies did not directly ascertain whether N-linked glycosylation was critical for ligand binding per se or whether it was actually required for the intracellular trafficking and surface expression of functionally active TPs on the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

The role of N-linked glycosylation in determining the surface expression, G protein interaction and effector coupling of the alpha (α) isoform of the human thromboxane A2 receptor

Kelley

Kinsella

2003

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Publication information Publisher's statementThis is the author's version of a work that was accepted for publication in Biochimica et Biophysica Acta. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta

show abstract

Tunicamycin inhibition of polyisoprenyl N-acetylglucosaminyl pyrophosphate formation in calf-liver microsomes

Cited by 844 publications

References 17 publications

Glycosylation and the activation of proteinase‐activated receptor 2 (PAR₂) by human mast cell tryptase

Glycosylation and the activation of proteinase‐activated receptor 2 (PAR₂) by human mast cell tryptase

Role of endoplasmic reticulum stress in drug‐induced toxicity

The role of N-linked glycosylation in determining the surface expression, G protein interaction and effector coupling of the alpha (α) isoform of the human thromboxane A2 receptor

Contact Info

Product

Resources

About

Tunicamycin inhibition of polyisoprenyl N-acetylglucosaminyl pyrophosphate formation in calf-liver microsomes

Cited by 844 publications

References 17 publications

Glycosylation and the activation of proteinase‐activated receptor 2 (PAR2) by human mast cell tryptase

Glycosylation and the activation of proteinase‐activated receptor 2 (PAR2) by human mast cell tryptase

Role of endoplasmic reticulum stress in drug‐induced toxicity

The role of N-linked glycosylation in determining the surface expression, G protein interaction and effector coupling of the alpha (α) isoform of the human thromboxane A2 receptor

Contact Info

Product

Resources

About

Glycosylation and the activation of proteinase‐activated receptor 2 (PAR₂) by human mast cell tryptase

Glycosylation and the activation of proteinase‐activated receptor 2 (PAR₂) by human mast cell tryptase