scholarly journals Adrenal Oncocytic Neoplasm with Paradoxical Loss of Important Mitochondrial Steroidogenic Protein: The 18 kDA Translocator Protein

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Alia Gupta ◽  
Arumugam R. Jayakumar ◽  
Gaetano Ciancio ◽  
Gunnlaugur Petur Nielsen ◽  
...  
Keyword(s):  
Internal Control ◽  
Clinical Manifestations ◽  
Significant Loss ◽  
Translocator Protein ◽  
Adrenal Cells ◽  
Rate Limiting Step ◽  
Adrenal Neoplasms ◽  
Oncocytic Tumor ◽  
Response To Stress ◽  
Oncocytic Neoplasm

The adrenal glands produce a variety of hormones that play a key role in the regulation of blood pressure, electrolyte homeostasis, metabolism, immune system suppression, and the body’s physiologic response to stress. Adrenal neoplasms can be asymptomatic or can overproduce certain hormones that lead to different clinical manifestations. Oncocytic adrenal neoplasms are infrequent tumors that arise from cells in the adrenal cortex and display a characteristic increase in the number of cytoplasmic mitochondria. Since the rate-limiting step in steroidogenesis includes the transport of cholesterol across the mitochondrial membranes, in part carried out by the 18-kDa translocator protein (TSPO), we assessed the expression of TSPO in a case of adrenal oncocytic neoplasm using residual adrenal gland of the patient as internal control. We observed a significant loss of TSPO immunofluorescence expression in the adrenal oncocytic tumor cells when compared to adjacent normal adrenal tissue. We further confirmed this finding by employing Western blot analysis to semiquantify TSPO expression in tumor and normal adrenal cells. Our findings could suggest a potential role of TSPO in the tumorigenesis of this case of adrenocortical oncocytic neoplasm.

scholarly journals Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management

2021 ◽  
Vol 10 (15) ◽  
pp. 3239
Author(s):  
Miguel A. Ortega ◽  
Oscar Fraile-Martínez ◽  
Cielo García-Montero ◽  
Miguel A. Álvarez-Mon ◽  
Chen Chaowen ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Current Knowledge ◽  
Varicose Veins ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Significant Loss ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Environmental Agents

Chronic venous disease (CVD) is a multifactorial condition affecting an important percentage of the global population. It ranges from mild clinical signs, such as telangiectasias or reticular veins, to severe manifestations, such as venous ulcerations. However, varicose veins (VVs) are the most common manifestation of CVD. The explicit mechanisms of the disease are not well-understood. It seems that genetics and a plethora of environmental agents play an important role in the development and progression of CVD. The exposure to these factors leads to altered hemodynamics of the venous system, described as ambulatory venous hypertension, therefore promoting microcirculatory changes, inflammatory responses, hypoxia, venous wall remodeling, and epigenetic variations, even with important systemic implications. Thus, a proper clinical management of patients with CVD is essential to prevent potential harms of the disease, which also entails a significant loss of the quality of life in these individuals. Hence, the aim of the present review is to collect the current knowledge of CVD, including its epidemiology, etiology, and risk factors, but emphasizing the pathophysiology and medical care of these patients, including clinical manifestations, diagnosis, and treatments. Furthermore, future directions will also be covered in this work in order to provide potential fields to explore in the context of CVD.

scholarly journals The Brain–Skin Axis in Psoriasis—Psychological, Psychiatric, Hormonal, and Dermatological Aspects

2022 ◽  
Vol 23 (2) ◽  
pp. 669
Author(s):  
Luiza Marek-Jozefowicz ◽  
Rafał Czajkowski ◽  
Alina Borkowska ◽  
Bogusław Nedoszytko ◽  
Michał A. Żmijewski ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Clinical Manifestations ◽  
Stress Signaling ◽  
Depression And Anxiety ◽  
Inflammatory Skin Disease ◽  
Skin Cells ◽  
Symptoms Of Depression ◽  
Functional Analog ◽  
Response To Stress ◽  
The Brain

Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches.

scholarly journals Persistent inflammation, immunosuppression and catabolism syndrome: mechanisms of sarcopenia and ways of correction

2021 ◽  
Vol 16 (7-8) ◽  
pp. 110-117
Author(s):  
S.M. Chuklin ◽  
S.S. Chuklin ◽  
G.V. Shershen
Keyword(s):  
Intensive Care ◽  
Critical Illness ◽  
Necrotizing Pancreatitis ◽  
Clinical Manifestations ◽  
Severe Trauma ◽  
Significant Loss ◽  
Mild Degree ◽  
Persistent Inflammation ◽  
Chronic Critical Illness ◽  
Severe Pathology

Due to advances in intensive care, many patients with severe pathology are discharged from intensive care units. However, prolonged mild degree inflammation persists in some patients, recovery is protracted, and chronic critical illness develops in them. In addition, persistent inflammation, immunosuppression and catabolism arise. In 2012, this condition was identified as a separate syndrome, which can be observed after severe trauma and burns, sepsis, necrotizing pancreatitis. Significant loss of muscle mass that is difficult to correct is one of the leading clinical manifestations in this case. Using literature from the MEDLINE database, modern ideas about the mechanisms of sarcopenia in the persistent inflammation, immunosuppression and catabolism syndrome and possible ways of optimal anabolic support are described.

scholarly journals Comorbidity in idiopathic pulmonary fibrosis - what can biomarkers tell us?

2020 ◽  
Vol 14 ◽  
pp. 175346662091009 ◽  
Author(s):  
Tiago M. Alfaro ◽  
Carlos Robalo Cordeiro
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Clinical Manifestations ◽  
Premature Death ◽  
Sleep Apnoea ◽  
Significant Loss ◽  
Diagnostic Methods ◽  
Response To Treatment ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive parenchymal scarring, leading to dyspnoea, respiratory failure and premature death. Although IPF is confined to the lungs, the importance of IPF comorbidities such as pulmonary hypertension and ischaemic heart disease, lung cancer, emphysema/chronic obstructive pulmonary disease, gastroesophageal reflux, sleep apnoea and depression has been increasingly recognized. These comorbidities may be associated with increased mortality and significant loss of quality of life, so their identification and management are vital. The development of good-quality biomarkers could lead to numerous gains in the management of these patients. Biomarkers can be used for the identification of predisposed individuals, early diagnosis, assessment of prognosis, selection of best treatment and assessment of response to treatment. However, the role of biomarkers for IPF comorbidities is still quite limited, and mostly based on evidence coming from populations without IPF. The future development of new biomarker studies could be informed by those that have been studied independently for each of these conditions. For now, clinicians should be mostly attentive to clinical manifestations of IPF comorbidities, and use validated diagnostic methods for diagnosis. As research on biomarkers of most common diseases continues, it is expected that useful biomarkers are developed for these diseases and then validated for IPF populations. The reviews of this paper are available via the supplemental material section.

scholarly journals TSPO mutations in rats and a human polymorphism impair the rate of steroid synthesis

2017 ◽  
Vol 474 (23) ◽  
pp. 3985-3999 ◽  
Author(s):  
David R. Owen ◽  
Jinjiang Fan ◽  
Enrico Campioli ◽  
Sathvika Venugopal ◽  
Andrew Midzak ◽  
...  
Keyword(s):  
Translocator Protein ◽  
Rat Tissues ◽  
Steroid Synthesis ◽  
Rate Limiting Step ◽  
Steroid Dependent ◽  
Proliferation And Apoptosis ◽  
Numerous Cell ◽  
Human Polymorphism ◽  
Hormone Biosynthesis ◽  
Rate Limiting

The 18 kDa translocator protein (TSPO) is a ubiquitous conserved outer mitochondrial membrane protein implicated in numerous cell and tissue functions, including steroid hormone biosynthesis, respiration, cell proliferation, and apoptosis. TSPO binds with high affinity to cholesterol and numerous compounds, is expressed at high levels in steroid-synthesizing tissues, and mediates cholesterol import into mitochondria, which is the rate-limiting step in steroid formation. In humans, the rs6971 polymorphism on the TSPO gene leads to an amino acid substitution in the fifth transmembrane loop of the protein, which is where the cholesterol-binding domain of TSPO is located, and this polymorphism has been associated with anxiety-related disorders. However, recent knockout mouse models have provided inconsistent conclusions of whether TSPO is directly involved in steroid synthesis. In this report, we show that TSPO deletion mutations in rat and its corresponding rs6971 polymorphism in humans alter adrenocorticotropic hormone-induced plasma corticosteroid concentrations. Rat tissues examined show increased cholesteryl ester accumulation, and neurosteroid formation was undetectable in homozygous rats. These results also support a role for TSPO ligands in diseases with steroid-dependent stress and anxiety elements.

scholarly journals Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans

2018 ◽  
Vol 115 (28) ◽  
pp. E6576-E6584 ◽  
Author(s):  
Henning Værøy ◽  
Csaba Adori ◽  
Romain Legrand ◽  
Nicolas Lucas ◽  
Jonathan Breton ◽  
...  
Keyword(s):  
Amino Acids ◽  
Adrenocorticotropic Hormone ◽  
Cortisol Secretion ◽  
Adrenal Cells ◽  
Igg Binding ◽  
History Of ◽  
Response To Stress ◽  
Underlying Mechanisms ◽  
Epitope Binding

Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11–24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1–13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident–intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors’ sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.

scholarly journals Expression of mycolic acid in response to stress and association with differential clinical manifestations of tuberculosis

2019 ◽  
Vol 8 (3) ◽  
pp. 237
Author(s):  
Mandira Varma-Basil ◽  
NareshKumar Sharma ◽  
Nisha Rathor ◽  
Rajesh Sinha ◽  
Shraddha Gupta ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Mycolic Acid ◽  
Response To Stress

The Pituitary Response to Stress: An Immunocytochemical - Cytophysiologic Study

1973 ◽  
Vol 31 ◽  
pp. 666-667
Author(s):  
Gwen C. Moriarty ◽  
C. M. Moriarty
Keyword(s):  
Electron Microscopy ◽  
Secretory Granules ◽  
Anterior Lobe ◽  
Intermediate Lobe ◽  
Adrenal Cells ◽  
Response To Stress ◽  
Parenchymal Cells ◽  
Unlabeled Antibody ◽  
Adrenalectomized Rats

Physiologic studies have shown that there is a peptide in mammalian neurointermediate lobes with immunologic and biologic properties similar to adrenocorticotropin (ACTH). Immunocytochemists have localized the peptide in the secretory granules of the intermediate lobe parenchymal cells and in rostral zone anterior lobe ACTH cells. [Moriarty, G. C. and Halmi, N. S., Z. Zellforsch 132:1 (1972)].In an attempt to determine the physiologic significance of this peptide, we rapidly removed the pituitaries from intact and adrenalectomized rats which were stressed by ether (2 minutes) or a buzzer (30 minutes). The neurointermediate lobes were separated from the anterior lobes and prepared for electron microscopy and immunocytochemistry (with the unlabeled antibody peroxidase-antiperoxidase complex technique) and ACTH bioassay (with the use of dispersed adrenal cells according to Sayers et al.) and radioimmunoassay.

Steroidogenic abnormalities in translocator protein knockout mice and significance in the aging male

2018 ◽  
Vol 475 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Anna M. Barron ◽  
Bin Ji ◽  
Seiji Kito ◽  
Tetsuya Suhara ◽  
Makoto Higuchi
Keyword(s):  
Young Male ◽  
Translocator Protein ◽  
Compensatory Mechanisms ◽  
Hormone Synthesis ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Adrenal Steroidogenesis ◽  
Age Dependent ◽  
Mitochondrial Cholesterol ◽  
Rate Limiting

The translocator protein (TSPO) has been proposed to act as a key component in a complex important for mitochondrial cholesterol importation, which is the rate-limiting step in steroid hormone synthesis. However, TSPO function in steroidogenesis has recently been challenged by the development of TSPO knockout (TSPO-KO) mice, as they exhibit normal baseline gonadal testosterone and adrenal corticosteroid production. Here, we demonstrate that despite normal androgen levels in young male TSPO-KO mice, TSPO deficiency alters steroidogenic flux and results in reduced total steroidogenic output. Specific reductions in the levels of progesterone and corticosterone as well as age-dependent androgen deficiency were observed in both young and aged male TSPO-KO mice. Collectively, these findings indicate that while TSPO is not critical for achieving baseline testicular and adrenal steroidogenesis, either indirect effects of TSPO on steroidogenic processes, or compensatory mechanisms and functional redundancy, lead to subtle steroidogenic abnormalities which become exacerbated with aging.

scholarly journals The New Dipeptide TSPO Ligands: Design, Synthesis and Structure–Anxiolytic Activity Relationship

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5132
Author(s):  
Tatiana A. Gudasheva ◽  
Olga A. Deeva ◽  
Andrey S. Pantileev ◽  
Grigory V. Mokrov ◽  
Inna V. Rybina ◽  
...  
Keyword(s):  
Amino Acid ◽  
Dose Range ◽  
Anxiolytic Effect ◽  
Anxiolytic Activity ◽  
Translocator Protein ◽  
Activity Relationship ◽  
Amino Acid Residues ◽  
Inner Mitochondrial Membrane ◽  
Design Synthesis ◽  
Rate Limiting Step

The translocator protein (TSPO, 18 kDa) plays an important role in the synthesis of neurosteroids by promoting the transport of cholesterol from the outer to the inner mitochondrial membrane, which is the rate-limiting step in neurosteroidogenesis. Stimulation of TSPO by appropriate ligands increases the level of neurosteroids. The present study describes the design, synthesis and investigation of anxiolytic-like effects of a series of N-acyl-tryptophanyl-containing dipeptides. These novel dipeptide TSPO ligands were designed with the original drug-based peptide design strategy using alpidem as non-peptide prototype. The anxiolytic activities were investigated in Balb/C mice using the illuminated open-field and elevated plus-maze tests in outbred laboratory mice ICR (CD-1). Dipeptide GD-102 (N-phenylpropionyl-l-tryptophanyl-l-leucine amide) in the dose range of 0.01–0.5 mg/kg intraperitoneally (i.p.) has a pronounced anxiolytic activity. The anxiolytic effect of GD-102 was abolished by PK11195, a specific TSPO antagonist. The structure–activity relationship study made it possible to identify a pharmacophore fragment for the dipeptide TSPO ligand. It was shown that l,d-diastereomer of GD-102 has no activity, and the d,l-isomer has less pronounced activity. The anxiolytic activity also disappears by replacing the C-amide group with the methyl ester, a free carboxyl group or methylamide. Consecutive replacement of each amino acid residue with glycine showed the importance of each of the amino acid residues in the structure of the ligand. The most active and technologically available compound GD-102, was selected for evaluation as a potential anxiolytic drug.

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