Altered ureido protein modification profiles in seminal plasma extracellular vesicles of non-normozoospermic men

Abstract

IntroductionExtracellular vesicles (EVs) have been recognized as key players in numerous physiological functions. These vesicles alter their compositions attuned to the health and disease states of the organism. In men, significant changes in the proteomic composition(s) of seminal plasma EVs (sEVs) have already been found to be related to infertility.MethodsMethods: In this study, we analyze the posttranslational configuration of sEV proteomes from normozoospermic (NZ) men and non-normozoospermic (non-NZ) men diagnosed with teratozoospermia and/or asthenozoospermia by unbiased, discovery-driven proteomics and advanced bioinformatics, specifically focusing on citrulline (Cit) and homocitrulline (hCit) posttranscriptional residues, both considered product of ureido protein modifications. Results and discussionSignificant increase in the proteome-wide cumulative presence of hCit together with downregulation of Cit in specific proteins related to decisive molecular functions have been encountered in sEVs of non-NZ subjects. These findings identify novel culprits with a higher chance of affecting fundamental aspects of sperm functional quality and define potential specific diagnostic and prognostic non-invasive markers for male infertility.

Trioxidized cysteine in the aging proteome mimics the structural dynamics and interactome of phosphorylated serine

“…At the molecular level, dysregulated phosphorylation‐mediated abnormal cellular signaling has been extensively associated with the influence of aging on these diseases (Ardito et al., 2017 ; Bilbrough et al., 2022 ; Gallart‐Palau et al., 2019 ). Similarly, increased oxidative stress is widely recognized to relate to aging and the onset and progression of these human disorders (Ebert et al., 2022 ; Liguori et al., 2018 ; Roy et al., 2023 ). However, the underlying molecular mechanism remains elusive.…”

“…Currently, over 700 PTMs have been identified, which significantly extend the proteome diversity of the organism (Jennings et al., 2022 ; Kalailingam et al., 2023 ). Phosphorylation is the most relevant PTM that plays a crucial role in regulating various cellular processes, including genome stability, proteostasis, cellular signaling, and cell metabolism (Hepowit et al., 2022 ; Johnson & Barford, 1993 ; Roy et al., 2023 ; Tarrant & Cole, 2009 ). This modification is facilitated by a family of enzymes known as protein kinases, which catalyze the addition of phosphate groups from ATP molecules to the specific protein amino acid residues serine (Ser), threonine (Thr), and tyrosine (Tyr; Audagnotto & Dal Peraro, 2017 ; Cohen, 2002 ; Mandell et al., 2007 ).…”

Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome

“…Dissected tissues were subsequently washed three times with 1× PBS for 30 min. Brain tissues from each neuroanatomical region and subject were randomly pooled to form three independent biological group replicates (n = 5; ~150 mg) per condition and neuroanatomical region, as we previously indicated [18,27]. Homogenization of dissected brain tissues was performed as previously described by our group [16] by using a Bullet Blender tissue homogenizer (Next Advance, Raymertown, NY, USA).…”

Differential systemic decellularization in vivo to study molecular changes in each vasculature layer in murine models of disease

“…Similarly, identification of the SMC markers such as smooth muscle actin alpha 2 (ACTA2) can be performed in SMC fraction collected as indicated. 1 If the DISDIVO collected sample are analyzed by systems biology, 6 proteins of the different systemic vascular beds can be identified and characterized, allowing the characterization of specific vascular beds such as the capillary vascular beds, brain vascular beds or liver vascular beds. Characterization of the obtained proteins may provide crucial information on the molecular compositions of the endothelium mantle within the capillary beds of these specific organs and systems.…”