Potentiation of the reductase activity of protein disulphide isomerase (PDI) by 19-nortestosterone, bacitracin, fluoxetine, and ammonium sulphate

Hassan, Maya Haj; Alvarez, Eva Rodriguez; Cahoreau, Claire; Klett, Danièle; Lecompte, François; Combarnous, Yves

doi:10.3109/14756366.2010.546794

Cited by 2 publications

(2 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A 90 to 95% inhibition was routinely measured in the presence of 5 mM Bac. The millimolar concentrations of Bac required for inhibition are within range of the reported concentrations for PDI inhibition (26,41,53,66). Control medium prepared with PMSF but lacking Bac showed no inhibition of infection, ruling out any effect from the PMSF hydrolysis products.…”

Section: Bacitracin Inhibition Of Hpv Infectionmentioning

confidence: 65%

See 1 more Smart Citation

Opposing Effects of Bacitracin on Human Papillomavirus Type 16 Infection: Enhancement of Binding and Entry and Inhibition of Endosomal Penetration

Campos

Chapman

Deymier

et al. 2012

J Virol

View full text Add to dashboard Cite

e Cell invasion by human papillomavirus type 16 (HPV16) is a complex process relying on multiple host cell factors. Here we describe an investigation into the role of cellular protein disulfide isomerases (PDIs) by studying the effects of the commonly used PDI inhibitor bacitracin on HPV16 infection. Bacitracin caused an unusual time-dependent opposing effect on viral infection. Enhanced cellular binding and entry were observed at early times of infection, while inhibition was observed at later times postentry. Bacitracin was rapidly taken up by host cells and colocalized with HPV16 at late times of infection. Bacitracin had no deleterious effect on HPV16 entry, capsid disassembly, exposure of L1/L2 epitopes, or lysosomal trafficking but caused a stark inhibition of L2/viral DNA (vDNA) endosomal penetration and accumulation at nuclear PML bodies. ␥-Secretase has recently been implicated in the endosomal penetration of L2/vDNA, but bacitracin had no effect on ␥-secretase activity, indicating that blockage of this step occurs through a ␥-secretase-independent mechanism. Transient treatment with the reductant ␤-mercaptoethanol (␤-ME) was able to partially rescue the virus from bacitracin, suggesting the involvement of a cellular reductase activity in HPV16 infection. Small interfering RNA (siRNA) knockdown of cellular PDI and the related PDI family members ERp57 and ERp72 reveals a potential role for PDI and ERp72 in HPV infection. Human papillomaviruses (HPVs) are one of the most common sexually transmitted infections in the world. HPVs are small 55-nm icosahedral nonenveloped double-stranded DNA (dsDNA) viruses that replicate in differentiating cutaneous and mucosal epithelium. Infection of mucosal epithelium by oncogenic HPV genotypes can lead to cervical, anogenital, and other head and neck cancers. HPV type 16 (HPV16) is the most common of the high-risk types and is alone responsible for over 50% of cervical cancers worldwide (77). Although HPVs have been known to be the etiological agent of cervical cancer for nearly 30 years, and despite intensive research in recent years, the infectious entry pathway of HPV16 is still not well defined. Our current understanding of HPV cellular invasion reveals a complex and prolonged process, complicated by differences between in vitro cell culture systems and the recently described in vivo mouse cervicovaginal challenge model (33,37,50,62).The HPV capsid is assembled from 360 molecules of the L1 protein, arranged as 72 pentamers. L1 monomers from neighboring pentamers are disulfide bonded to each other as dimers and trimers, providing stability to the capsid (45). The minor capsid protein L2 is localized within a central cavity beneath the L1 pentamers. L2 can be present at a maximum stoichiometry of one L2 molecule per L1 pentamer or 72 molecules per virion; however, most preparations of virus contain submaximal levels of L2, typically 20 to 25 copies per virion (6). Packaged within the capsid is the ϳ8-kb viral genome (viral DNA [vDNA]), condensed as chromatin with cellu...

show abstract

Section: Bacitracin Inhibition Of Hpv Infectionmentioning

confidence: 65%

“…Although Bac is not a specific inhibitor of PDIs, it has been reported to inhibit the reductive function of PDI by a number of different cell-based and in vitro assays (26,35,41,66). We therefore hypothesized that the addition of the cell-permeant reductant ␤-mercaptoethanol (␤-ME) might relieve the inhibition caused by Bac.…”

Section: Figmentioning

confidence: 99%

Opposing Effects of Bacitracin on Human Papillomavirus Type 16 Infection: Enhancement of Binding and Entry and Inhibition of Endosomal Penetration

Campos

Chapman

Deymier

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

Epididymal mRNA expression profiles for the protein disulfide isomerase gene family: Modulation by development and androgens

Fernandes,

Ferreira,

Benham

et al. 2024

Andrology

View full text Add to dashboard Cite

BackgroundThe endoplasmic reticulum (ER) is the central hub for protein quality control, where the protein disulfide isomerases (PDIs), encoded by at least 21 genes, play a pivotal role. These multifunctional proteins contribute to disulfide bond formation, proper folding, and protein modifications, and may act as hormone‐binding proteins (e.g., steroids), influencing hormone biology. The interplay between ER proteostasis, PDIs, and epididymis—a crucial site for sperm maturation—remains largely understudied.ObjectivesThis study characterizes transcriptional signatures of Pdi genes in the epididymis.Material and methodsTranscriptional profiles of selected Pdi genes were assessed in adult Wistar rat tissues, and epididymis under different experimental conditions (developmental stages, surgical castration, and efferent ductules ligation [EDL]). In silico bioinformatic analyses identified expression trends of this gene family in human epididymal segments.ResultsP4hb, Pdia3, Pdia5, Pdia6, Erp44, Erp29, and Casq1 transcripts were detected in both reproductive and non‐reproductive tissues, while Casq2 exhibited higher abundance in vas deferens, prostate, and heart. Pdilt, highly expressed in testis, and Pdia2, highly expressed in heart, showed minimal mRNA levels in the epididymis. In the mesonephric duct, epididymal embryonic precursor, P4hb, Pdia3, Pdia5, Pdia6, and Erp29 mRNAs were found at gestational day (GD) 17.5. Except for Erp29, which remained stable, these Pdi transcript levels increased from GD17.5 to GD20.5, when epididymal morphogenesis occurs, and were maintained to varying degrees in the epididymis during postnatal development. Surgical castration downregulated P4hb, Pdia3, Pdia5, Pdia6, Pdilt and Erp29 transcripts, an effect reversed by testosterone replacement. Conversely, transcript levels remained unaffected by EDL, except P4hb, which was reduced in caput epididymis. All 21 PDI genes exhibited diverse transcriptional profiles across the human epididymis.Discussion and conclusionThe findings lay the foundations to explore Pdi genes in epididymal biology. As a considerable proportion of male infertility cases are idiopathic, targeting hormonal regulation of protein quality control in epididymis represents a route to address male infertility and advance therapeutic interventions in this domain.

show abstract

Potentiation of the reductase activity of protein disulphide isomerase (PDI) by 19-nortestosterone, bacitracin, fluoxetine, and ammonium sulphate

Cited by 2 publications

References 41 publications

Opposing Effects of Bacitracin on Human Papillomavirus Type 16 Infection: Enhancement of Binding and Entry and Inhibition of Endosomal Penetration

Opposing Effects of Bacitracin on Human Papillomavirus Type 16 Infection: Enhancement of Binding and Entry and Inhibition of Endosomal Penetration

Epididymal mRNA expression profiles for the protein disulfide isomerase gene family: Modulation by development and androgens

Contact Info

Product

Resources

About