Differential Post-Translational Modifications of Proteins in Bladder Ischemia.

Clinical and basic research suggests that bladder ischemia may be an independent variable in the development of lower urinary tract symptoms (LUTS). We have reported that ischemic changes in the bladder involve differential expression and post-translational modifications (PTMs) of the protein's functional domains. In the present study, we performed in-depth analysis of a previously reported proteomic dataset to further characterize proteins PTMs in bladder ischemia.

Molecular Regulation of Concomitant Lower Urinary Tract Symptoms and Erectile Dysfunction in Pelvic Ischemia.

Aging correlates with greater incidence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in the male population where the pathophysiological link remains elusive. The incidence of LUTS and ED correlates with the prevalence of vascular risk factors, implying potential role of arterial disorders in concomitant development of the two conditions. Human studies have revealed lower bladder and prostate blood flow in patients with LUTS suggesting that the severity of LUTS and ED correlates with the severity of vascular disorders.

Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia.

Purpose: Growing evidence suggests that ischemia provokes detrusor overactivity and degenerative responses in the bladder. Underlying mechanisms appear to involve modification of smooth muscle contractile rudiments by hypoxia, redox, cellular stress and cell survival signaling. Downstream pathways of cellular stress and stress response molecules eliciting bladder dysfunction in ischemia remain largely elusive.

Cellular Stress and Molecular Responses in Bladder Ischemia.

The concept of bladder ischemia as a contributing factor to detrusor overactivity and lower urinary tract symptoms (LUTS) is evolving. Bladder ischemia as a consequence of pelvic arterial atherosclerosis was first documented in experimental models and later in elderly patients with LUTS. It was shown that early-stage moderate ischemia produces detrusor overactivity, while prolonged severe ischemia provokes changes consistent with detrusor underactivity.

Impairment of AMPK-α2 augments detrusor contractions in bladder ischemia.

Purpose: Ischemia disrupts cellular energy homeostasis. Adenosine monophosphate-activated protein kinase alpha-2 (AMPK-α2) is a subunit of AMPK that senses cellular energy deprivation and signals metabolic stress. Our goal was to examine the expression levels and functional role of AMPK-α2 in bladder ischemia.

Post-Translational Modification Networks of Contractile and Cellular Stress Response Proteins in Bladder Ischemia.

Molecular mechanisms underlying bladder dysfunction in ischemia, particularly at the protein and protein modification levels and downstream pathways, remain largely unknown. Here we describe a comparison of protein sequence variations in the ischemic and normal bladder tissues by measuring the mass differences of the coding amino acids and actual residues crossing the proteome. A large number of nonzero delta masses (11,056) were detected, spanning over 1295 protein residues.

Regulation of Cellular Stress Signaling in Bladder Ischemia.

Introduction: The etiology of lower urinary tract symptoms in patients with non-obstructed non-neurogenic bladder remains largely unknown. Clinical studies divulged a significant correlation between reduced bladder blood flow and low bladder compliance. Animal models of bladder ischemia displayed structural modifications, characterized by loss of smooth muscle cells and accumulation of connective tissue in the bladder wall.

Post-Translational Modification of Human Histone by Wide Tolerance of Acetylation.

Histone acetylation adds an acetyl group on the lysine residue commonly found within the N-terminal tail protruding from the histone core of the nucleosome, and is important for chromosome structure and function in gene transcription and chromatin remodeling. Acetylation may also occur on other residues additional to lysine, but have not been thoroughly investigated at the proteomics level. Here we report a wide tolerance acetylation study mimicking the addition of 42 ± 0.

Mitochondrial stress and activation of PI3K and Akt survival pathway in bladder ischemia.

Purpose: Detrusor overactivity contributes to bothersome constellation of lower urinary tract symptoms (LUTS) in men and women as they age. However, the underlying mechanisms of non-obstructive detrusor overactivity and LUTS remain largely unknown. Growing evidence suggests that ischemia may be an independent factor in the development of non-obstructive bladder dysfunction.

LC-MS/MS Analysis Unravels Deep Oxidation of Manganese Superoxide Dismutase in Kidney Cancer.

Manganese superoxide dismutase (MNSOD) is one of the major scavengers of reactive oxygen species (ROS) in mitochondria with pivotal regulatory role in ischemic disorders, inflammation and cancer. Here we report oxidative modification of MNSOD in human renal cell carcinoma (RCC) by the shotgun method using data-dependent liquid chromatography tandem mass spectrometry (LC-MS/MS). While 5816 and 5571 proteins were identified in cancer and adjacent tissues, respectively, 208 proteins were found to be up- or down-regulated ( < 0.

Yersinia pestis acetyltransferase-mediated dual acetylation at the serine and lysine residues enhances the auto-ubiquitination of ubiquitin ligase MARCH8 in human cells.

Lysine acetylation is known as a post translational modification (PTM) by histone acetyltransferases (HAT) that modifies histones and non-histone proteins to regulate gene expression. Serine acetylation, however, is reported in mammalian hosts by serine acetyltransferase of Yersinia pestis (YopJ) during infection. The protein target and cellular function of bacterial YopJ in mammalian systems are not fully addressed.

Corrigendum: Correction of title spelling. Progressive changes in detrusor function and micturition patterns with chronic bladder ischemia.

[This corrects the article on p. 249 in vol. 57.

Progressive changes in detrusor function and micturition patterns with chronic bladder ischemia.

Purpose: Lower urinary tract symptoms (LUTS) are bothersome constellation of voiding symptoms in men and women as they age. Multiple factors and comorbidities are attributed to this problem but underlying mechanisms of nonobstructive nonneurogenic detrusor overactivity, detrusor underactivity and LUTS remain largely unknown. Our goal was to characterize detrusor function and voiding patterns in relation to muscarinic receptors expression, nerve fiber density, and neural ultrastructure in chronic bladder ischemia.

Unraveling molecular effects of ADAR1 overexpression in HEK293T cells by label-free quantitative proteomics.

ADAR1 is a double-stranded RNA (dsRNA) editing enzyme that specifically converts adenosine to inosine. ADAR1 is ubiquitously expressed in eukaryotes and participate in various cellular processes such as differentiation, proliferation and immune responses. We report here a new proteomics study of HEK293T cells with and without ADAR1 overexpression.

Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis.

Viruses induce double-stranded RNA (dsRNA) in the host cells. The mammalian system has developed dsRNA-dependent recognition receptors such as RLRs that recognize the long stretches of dsRNA as PAMPs to activate interferon-mediated antiviral pathways and apoptosis in severe infection. Here we report an efficient antiviral immune response through dsRNA-dependent RLR receptor-mediated necroptosis against infections from different classes of viruses.

Alu RNA accumulation in hyperglycemia augments oxidative stress and impairs eNOS and SOD2 expression in endothelial cells.

Endothelial dysfunction resulting from oxidative stress and inflammation plays a dominant role in hyperglycemia-induced vasculopathy. While double-stranded RNA (dsRNA) accumulates in redox and inflammatory conditions, its precise role in hyperglycemia-associated endothelial dysfunction remains unclear. This study aimed to investigate whether and how endogenous dsRNA contributes to endothelial dysfunction via oxidative stress.

Unraveling Molecular Differences of Gastric Cancer by Label-Free Quantitative Proteomics Analysis.

Gastric cancer (GC) has significant morbidity and mortality worldwide and especially in China. Its molecular pathogenesis has not been thoroughly elaborated. The acknowledged biomarkers for diagnosis, prognosis, recurrence monitoring and treatment are lacking.

LUTS in pelvic ischemia: a new concept in voiding dysfunction.

Lower urinary tract symptoms (LUTS) are a group of voiding symptoms affecting both genders as they age. Traditionally, LUTS in men were commonly attributed to bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE). It was later shown that, in approximately one-third to more than one-half of cases, LUTS in men are not associated with BOO.

Quantitative Proteomic Analysis of Differentially Expressed Proteins and Downstream Signaling Pathways in Chronic Bladder Ischemia.

Purpose: Growing evidence suggests that ischemia may contribute to aging associated bladder dysfunction and lower urinary tract symptoms. Our goal was to determine the effects of chronic ischemia on bladder proteomic profiles and characterize downstream signaling pathways.

Materials And Methods: Bilateral iliac artery atherosclerosis and chronic bladder ischemia were created in male Sprague Dawley® rats.

Structural modifications of the prostate in hypoxia, oxidative stress, and chronic ischemia.

Purpose: Clinical studies have reported a correlation between pelvic ischemia and voiding dysfunction in elderly men. The aim of this study was to identify and compare prostate structural modifications in cultured cells and in a rabbit model after exposure to hypoxia, oxidative stress, and chronic ischemia.

Materials And Methods: Cultured human prostate smooth muscle cells (SMCs), epithelial cells (ECs), and stromal cells (SCs) were incubated under normoxia, hypoxia, and oxidative stress conditions by use of a computerized oxycycler system.

Could nocturia be an indicator of an undiagnosed sleep disorder in male veterans?

Objective: To determine if men presenting with nocturia and/or voiding complaints may have undiagnosed symptoms of sleep-disordered breathing (SDB).

Materials And Methods: We conducted a cross-sectional study with men presenting to the Veterans Administration Boston Healthcare System Urology clinic between August 2012 and January 2013. Patients were asked to complete the American Urological Association symptom score and the Berlin sleep questionnaire to evaluate their voiding complaints and sleep quality.

A novel IgM-H-ficolin complement pathway to attack allogenic cancer cells in vitro.

The pentameric serum IgMs are critical to immune defense and surveillance through cytotoxicity against microbes and nascent cancer cells. Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis. It remains unknown whether serum IgMs interplay with ficolins in cancer immunosurveillance.

Bladder oxidative stress in sleep apnea contributes to detrusor instability and nocturia.

Purpose: Obstructive sleep apnea is associated with voiding symptoms in humans and animals, and yet its effects on the urinary tract are poorly understood. We examined bladder structure and function, markers of oxidative damage and the redox survival pathway in a rat model of obstructive sleep apnea to identify changes.

Materials And Methods: To model obstructive sleep apnea we used a rat oxycycler system to create cyclical interruption in breathing oxygen, thereby producing intermittent hypoxemia.

Effects of ischemia and oxidative stress on bladder purinoceptors expression.

Objective: To study the effects of chronic ischemia on bladder purinoceptors. A close correlation between bladder ischemia and lower urinary tract symptoms has been reported. Purinoceptors contribute to important aspects of bladder function including sensation, neural signaling, and voiding contraction.