HIV-1 Enhancing Effect of Prostatic Acid Phosphatase Peptides Is Reduced in Human Seminal Plasma

Background: A well-known tissue marker of ovarian cancer, Human Epididymis protein 4 (HE4) is the member of whey acidic four-disulfide core proteins family. Purified from human seminal plasma and characterized as a cross-class protease inhibitor, HE4 was proposed to shield spermatozoa against proteolytic factors. However, its exact biological function is unknown. Proteins usually function in conjunction with other proteins in the system and thus, identification and analysis of protein networks become essential to decode protein functions. Objective: This study was performed to explore possible role(s) of HE4 in reproductive physiology via identification of its interactome in human seminal plasma. Methods: HE4 binding proteins were identified through co-immunoprecipitation and MALDITOF/ MS analysis. Also, HE4 was quantified by ELISA in fertile and infertile human seminal plasma samples. Results: Ten HE4 binding proteins were identified, viz. protein phosphatase 1 regulatory subunit 21, protein kinase CLK3, Ankyrin repeat domain-containing protein36A, prostatic acid phosphatase, KIF5C, Spectrin repeat containing, nuclear envelope 1, isoform CRAf, tropomyosin 4, vezatin, utrophin and fibronectin1. This interaction network suggests that HE4 plays multiple roles, specifically in capacitation, sperm motility and maturation. Further, HE4 concentration in human seminal plasma samples was determined by Elisa. Higher HE4 expression in normozoospermia compared to azoospermia and asthenozoospermia affirms its importance in fertilization. Conclusion: Based on identified interactome, it is plausible that HE4 plays a crucial role in fertilization, specifically in sperm maturation, motility and capacitation.

Download Full-text

Simple, rapid determination of zinc and acid phosphatase in seminal plasma with an ABA-100 bichromatic analyzer.

Clinical Chemistry ◽

10.1093/clinchem/34.8.1605 ◽

1988 ◽

Vol 34 (8) ◽

pp. 1605-1607 ◽

Cited By ~ 11

Author(s):

M Gavella

Keyword(s):

Acid Phosphatase ◽

Male Infertility ◽

Seminal Plasma ◽

Rapid Determination ◽

Assay System ◽

Human Seminal Plasma ◽

Automated Assay ◽

Sensitivity Specificity

Abstract I describe an automated assay for zinc and acid phosphatase in seminal plasma. These, which are markers of the function of the prostate, were assayed bichromatically with an Abbott ABA-100 analyzer. As many as 25 samples of human seminal plasma can be analyzed sequentially with CVs of 3.1% for zinc and 1.5% for acid phosphatase. The sensitivity, specificity, and speed of this assay system make it practicable for use in investigation of male infertility.

Download Full-text

Isolation and Identification of Concanavalin A Binding Glycoproteins from Human Seminal Plasma: A Step Towards Identification of Male Infertility Marker Proteins

Disease Markers ◽

10.1155/2011/798072 ◽

2011 ◽

Vol 31 (6) ◽

pp. 379-386 ◽

Cited By ~ 11

Author(s):

Anil Kumar Tomar ◽

Balwinder Singh Sooch ◽

Isha Raj ◽

Sarman Singh ◽

Tej P. Singh ◽

...

Keyword(s):

Male Infertility ◽

Seminal Plasma ◽

Concanavalin A ◽

Specific Antigen ◽

Clinical Importance ◽

Prostatic Acid Phosphatase ◽

Human Seminal Plasma ◽

Isolation And Identification ◽

Altered Expression ◽

Marker Proteins

Human seminal plasma contains a large array of proteins of clinical importance which are essentially needed to maintain the reproductive physiology of spermatozoa and for successful fertilization. Thus, isolation and identification of seminal plasma proteins is of paramount significance for their biophysical characterization and functional analysis in reproductive physiological processes. In this study, we have isolated Concanavalin-A binding glycoproteins from human seminal plasma and subsequently identified them by MALDI-TOF/MS analysis. The major proteins, as identified in this study, are Aminopeptidase N, lactoferrin, prostatic acid phosphatase, zinc-alpha-2-glycoprotein, prostate specific antigen, progestagen-associated endometrial protein, Izumo sperm-egg fusion protein and prolactin inducible protein. This paper also reports preliminary studies to identify altered expression of these proteins in oligospermia and azoospermia in comparison to normospermia. In oligospermia, five proteins were found to be downregulated while in azoospermia, four proteins were downregulated and two proteins were upregulated. Thus, this study is of immense biomedical interest towards identification of potential male infertility marker proteins in seminal plasma.

Download Full-text

Human Seminal Plasma Abrogates the Capture and Transmission of Human Immunodeficiency Virus Type 1 to CD4+ T Cells Mediated by DC-SIGN

Journal of Virology ◽

10.1128/jvi.01079-07 ◽

2007 ◽

Vol 81 (24) ◽

pp. 13723-13734 ◽

Cited By ~ 50

Author(s):

Juan Sabatté ◽

Ana Ceballos ◽

Silvina Raiden ◽

Mónica Vermeulen ◽

Karen Nahmod ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Seminal Plasma ◽

Intercellular Adhesion Molecule ◽

Target Cells ◽

Human Seminal Plasma ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is expressed by dendritic cells (DCs) at mucosal surfaces and appears to play an important role in the dissemination of human immunodeficiency virus type 1 (HIV-1) infection. DC-SIGN binds HIV-1 gp120 and efficiently transmits the virus to T CD4+ cells, which become the center of viral replication. Semen represents the main vector for HIV-1 dissemination worldwide. In the present study we show that human seminal plasma (SP), even when used at very high dilutions (1:104 to 1:105), markedly inhibits the capture and transmission of HIV-1 to T CD4+ cells mediated by both DCs and B-THP-1-DC-SIGN cells. In contrast, SP does not inhibit the capture of HIV-1 by DC-SIGN-negative target cells, such as the T-cell line SupT-1, monocytes, and activated peripheral blood mononuclear cells. The SP inhibitor has a high molecular mass (>100 kDa) and directly interacts with DC-SIGN-positive target cells but not with HIV-1. Moreover, the inhibitor binds to concanavalin A, suggesting that it contains high-mannose N-linked carbohydrates. Of note, using biotin-labeled SP we found that the binding of SP components to DCs was abrogated by mannan, while their interaction with B-THP-1 cells was almost completely dependent on the expression of DC-SIGN. Since epithelium integrity is often compromised after vaginal or anal intercourse, as well as in the presence of ulcerative-sexually transmitted diseases, our results support the notion that components of the SP might be able to access to the subepithelium, inhibiting the recognition of HIV-1 gp120 by DC-SIGN-positive DCs.

Download Full-text

Dual concentration-dependent effect of Ascorbic acid on PAP(248-286) amyloid formation and SEVI-mediated HIV infection

RSC Chemical Biology ◽

10.1039/d1cb00084e ◽

2021 ◽

Author(s):

Daniel Segal ◽

Jan Munch ◽

Ashim Paul ◽

elad arad ◽

Raz Jelinek ◽

...

Keyword(s):

Ascorbic Acid ◽

Acid Phosphatase ◽

Hiv Infection ◽

Prostatic Acid Phosphatase ◽

Amyloid Formation ◽

Human Semen ◽

Dependent Effect ◽

Amyloidogenic Peptides ◽

Hiv 1

Human semen contains various amyloidogenic peptides derived from Prostatic Acid Phosphatase (PAP) and Semenogelin proteins that are capable of enhancing HIV-1 infection when assembled into fibrils. The best characterized among...

Download Full-text

Seminal Plasma Accelerates Semen-derived Enhancer of Viral Infection (SEVI) Fibril Formation by the Prostatic Acid Phosphatase (PAP248–286) Peptide

Journal of Biological Chemistry ◽

10.1074/jbc.m111.314336 ◽

2012 ◽

Vol 287 (15) ◽

pp. 11842-11849 ◽

Cited By ~ 36

Author(s):

Joanna S. Olsen ◽

John T. M. DiMaio ◽

Todd M. Doran ◽

Caitlin Brown ◽

Bradley L. Nilsson ◽

...

Keyword(s):

Acid Phosphatase ◽

Viral Infection ◽

Seminal Plasma ◽

Amyloid Fibrils ◽

Divalent Cations ◽

Prostatic Acid Phosphatase ◽

Fibril Formation ◽

Amyloid Formation ◽

Precursor Peptide

Amyloid fibrils contained in semen, known as SEVI, or semen-derived enhancer of viral infection, have been shown to increase the infectivity of HIV dramatically. However, previous work with these fibrils has suggested that extensive time and nonphysiologic levels of agitation are necessary to induce amyloid formation from the precursor peptide (a proteolytic cleavage product of prostatic acid phosphatase, PAP248–286). Here, we show that fibril formation by PAP248–286is accelerated dramatically in the presence of seminal plasma (SP) and that agitation is not required for fibrillization in this setting. Analysis of the effects of specific SP components on fibril formation by PAP248–286revealed that this effect is primarily due to the anionic buffer components of SP (notably inorganic phosphate and sodium bicarbonate). Divalent cations present in SP had little effect on the kinetics of fibril formation, but physiologic levels of Zn2+strongly protected SEVI fibrils from degradation by seminal proteases. Taken together, these data suggest that in thein vivoenvironment, PAP248–286is likely to form fibrils efficiently, thus providing an explanation for the presence of SEVI in human semen.

Download Full-text