scholarly journals Stage-specific Localization and Expression of c-kit in the Adult Human Testis

2009 ◽  
Vol 57 (9) ◽  
pp. 861-869 ◽  
Author(s):  
Sreepoorna K. Unni ◽  
Deepak N. Modi ◽  
Shilpa G. Pathak ◽  
Jayesh V. Dhabalia ◽  
Deepa Bhartiya
Keyword(s):  
Current Knowledge ◽  
Protein Localization ◽  
Immunohistochemical Analysis ◽  
Human Testis ◽  
Specific Expression ◽  
Adult Human ◽  
Kit Receptor ◽  
Specific Localization ◽  
Human Spermatogenesis ◽  
And Function

The c-kit receptor (KIT) and its ligand, stem cell factor (SCF), represent one of the key regulators of testicular formation, development, and function and have been extensively studied in various animal models. The present study was undertaken to characterize the pattern of localization and expression of c-kit in normal adult human testis. Immunohistochemical analysis showed that KIT is expressed in the cytoplasm of spermatogonia, acrosomal granules of spermatids, and Leydig cells. Interestingly, a rather heterogenous pattern of expression of the protein along the basement membrane was observed. Intense protein localization in spermatogonia was detected in stages I–III, whereas low expression was observed in stages IV–VI of the seminiferous epithelium, indicating that the expression of the molecule was stage specific. In situ hybridization studies revealed that the transcripts of the gene were also localized in a similar non-uniform pattern. To the best of our knowledge, such a stage-specific expression of KIT has not been reported previously in the human testis. The results of the present study may expand current knowledge about the c-kit/SCF system in human spermatogenesis.

scholarly journals Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity

2009 ◽  
Vol 296 (6) ◽  
pp. F1307-F1313 ◽  
Author(s):  
Li Xia ◽  
Mingyan Zhou ◽  
Thomas F. Kalhorn ◽  
Horace T. B. Ho ◽  
Joanne Wang
Keyword(s):  
Cellular Localization ◽  
Organic Cation ◽  
Kidney Injury ◽  
Organic Cation Transporter ◽  
Intracellular Loop ◽  
Puromycin Aminonucleoside ◽  
Specific Expression ◽  
Specific Localization ◽  
Immunofluorescence Labeling ◽  
And Function

Plasma membrane monoamine transporter (PMAT) is a novel polyspecific organic cation transporter that transports organic cations and the purine nucleoside, adenosine. PMAT is expressed in the kidney, but the specific localization and function of this transporter in renal cells are unclear. In this study, we developed a polyclonal antibody toward a 14-amino acid sequence in the last intracellular loop of PMAT and determined the precise cellular localization of PMAT in human and rat kidneys. Surprisingly, we found that the PMAT protein was predominantly expressed in the glomerulus with minimal expression in tubular cells. Within the glomerulus, dual-color immunofluorescence labeling showed that the PMAT protein was specifically localized to the visceral glomerular epithelial cells, i.e., podocytes. There was no significant PMAT immunoreactivity in mesangial or glomerular endothelial cells. We further showed that puromycin aminonucleoside (PAN), a classic podocyte toxin that induces massive proteinuria and severe glomerulopathy, is transported by PMAT. Expression of PMAT in Madin-Darby canine kidney cells significantly increased cell sensitivity to PAN. Decynium 22, a potent PMAT inhibitor, abolished PAN toxicity in PMAT-expressing cells. Together, our data suggest that PMAT is specifically expressed in podocytes and may play an important role in PAN-induced kidney injury.

Intricate Regulation of Phosphoenolpyruvate Carboxykinase (PEPCK) Isoforms in Normal Physiology and Disease

2019 ◽  
Vol 19 (4) ◽  
pp. 247-272 ◽  
Author(s):  
Venu Seenappa ◽  
Manjunath B. Joshi ◽  
Kapaettu Satyamoorthy
Keyword(s):  
Translational Regulation ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Current Knowledge ◽  
Regulatory Elements ◽  
Copy Number Variations ◽  
Specific Expression ◽  
Physiological Processes ◽  
Clade B ◽  
And Function ◽  
Endogenous Modulators

Background:The phosphoenolpyruvate carboxykinase (PEPCK) isoforms are considered as rate-limiting enzymes for gluconeogenesis and glyceroneogenesis pathways. PEPCK exhibits several interesting features such as a) organelle-specific isoforms (cytosolic and a mitochondrial) in vertebrate clade, b) tissue-specific expression of isoforms and c) organism-specific requirement of ATP or GTP as a cofactor. In higher organisms, PEPCK isoforms are intricately regulated and activated through several physiological and pathological stimuli such as corticoids, hormones, nutrient starvation and hypoxia. Isoform-specific transcriptional/translational regulation and their interplay in maintaining glucose homeostasis remain to be fully understood. Mounting evidence indicates the significant involvement of PEPCK isoforms in physiological processes (development and longevity) and in the progression of a variety of diseases (metabolic disorders, cancer, Smith–Magenis syndrome).Objective:The present systematic review aimed to assimilate existing knowledge of transcriptional and translational regulation of PEPCK isoforms derived from cell, animal and clinical models.Conclusion:Based on current knowledge and extensive bioinformatics analysis, in this review we have provided a comparative (epi)genetic understanding of PCK1 and PCK2 genes encompassing regulatory elements, disease-associated polymorphisms, copy number variations, regulatory miRNAs and CpG densities. We have also discussed various exogenous and endogenous modulators of PEPCK isoforms and their signaling mechanisms. A comprehensive review of existing knowledge of PEPCK regulation and function may enable identification of the underlying gaps to design new pharmacological strategies and interventions for the diseases associated with gluconeogenesis.

scholarly journals Cloning and expression of a novel CREB mRNA splice variant in human testis

Reproduction ◽  
2004 ◽  
Vol 128 (6) ◽  
pp. 775-782 ◽  
Author(s):  
Xiaoyan Huang ◽  
Jun Zhang ◽  
Li Lu ◽  
Lanlan Yin ◽  
Min Xu ◽  
...  
Keyword(s):  
Splice Variant ◽  
Cloning And Expression ◽  
Human Testis ◽  
Genome Database ◽  
Adult Human ◽  
Element Binding Protein ◽  
Testis Cdna ◽  
Responsive Element ◽  
And Function ◽  
Camp Responsive Element Binding

Identification of genes specifically expressed in adult and fetal testis is important in furthering our understanding of testis development and function. In this study, a novel human transcript, designated human testis cAMP-responsive element-binding protein (htCREB), was identified by hybridization of adult and fetal human testis cDNA probes with a human cDNA microarray containing 9216 clones. The htCREB transcript (GenBank Accession no. AY347527) was expressed at 2.35-fold higher levels in adult human testes than in fetal testes. Sequence and ntBLAST analyses against the human genome database indicated that htCREB was a novel splice variant of human CREB. RT-PCR-based tissue distribution experiments demonstrated that the htCREB transcript was highly expressed in adult human testis and in healthy sperm, but not in testes from patients with Sertoli cell-only syndrome. Taken together, these results suggest that the htCREB transcript is chiefly expressed in germ cells and is most likely involved in spermatogenesis.

scholarly journals Runx transcription factors in the development and function of the definitive hematopoietic system

Blood ◽  
2017 ◽  
Vol 129 (15) ◽  
pp. 2061-2069 ◽  
Author(s):  
Marella de Bruijn ◽  
Elaine Dzierzak
Keyword(s):  
Transcription Factors ◽  
Current Knowledge ◽  
Biological Effects ◽  
Regulation Of Gene Expression ◽  
Loss Of Function ◽  
Specific Expression ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
Cell Lineages ◽  
And Function

AbstractThe Runx family of transcription factors (Runx1, Runx2, and Runx3) are highly conserved and encode proteins involved in a variety of cell lineages, including blood and blood-related cell lineages, during developmental and adult stages of life. They perform activation and repressive functions in the regulation of gene expression. The requirement for Runx1 in the normal hematopoietic development and its dysregulation through chromosomal translocations and loss-of-function mutations as found in acute myeloid leukemias highlight the importance of this transcription factor in the healthy blood system. Whereas another review will focus on the role of Runx factors in leukemias, this review will provide an overview of the normal regulation and function of Runx factors in hematopoiesis and focus particularly on the biological effects of Runx1 in the generation of hematopoietic stem cells. We will present the current knowledge of the structure and regulatory features directing lineage-specific expression of Runx genes, the models of embryonic and adult hematopoietic development that provide information on their function, and some of the mechanisms by which they affect hematopoietic function.

scholarly journals Analysis of activin/TGFB-signaling modulators within the normal and dysfunctional adult human testis reveals evidence of altered signaling capacity in a subset of seminomas

Reproduction ◽  
2009 ◽  
Vol 138 (5) ◽  
pp. 801-811 ◽  
Author(s):  
Vinali L Dias ◽  
Ewa Rajpert-De Meyts ◽  
Robert McLachlan ◽  
Kate Lakoski Loveland
Keyword(s):  
Growth Factor ◽  
Cellular Localization ◽  
Transforming Growth Factor ◽  
Male Gamete ◽  
Transforming Growth Factor Β ◽  
Human Testis ◽  
Adult Human ◽  
Normal Men ◽  
And Function ◽  
Tgfb Signaling

Activin is a pleiotropic growth factor belonging to the transforming growth factor-β (TGFB) superfamily of signaling molecules. Regulated activin signaling is known to influence several steps in rodent male gamete differentiation. TGFB ligand isoforms, TGFB1–B3, also influence germ cell survival in the rodent testis at the onset of spermatogenesis and around the time of puberty. Given the importance of regulated activin and TGFB signaling in testis development and function, we sought to investigate the cellular production sites of activin/TGFB-signaling modulators in normal and dysfunctional adult human testes samples. Signaling transducers phosphorylated SMAD2/3, and signaling modulators SMAD6, MAN-1, inhibin α (INHA), and β-glycan were detected in Bouins fixed, paraffin–embedded adult human testis sections using immunohistochemistry. Additional samples examined were from testicular cancer patients and from normal men subjected to gonadotropin suppression with androgen-based contraceptives. Our findings identify distinct differences between normal and gonadotropin-deprived human testis in the expression and cellular localization of activin/TGFB-signaling modulators. The presence of a nuclear phosphorylated SMAD2/3 signal in all analyzed seminoma specimens indicated active activin/TGFB signaling. Moreover, a subset of seminoma specimens exhibited selective enhanced expression of β-glycan (4 out of 28 seminoma tumors), INHA (6 out of 28), and MAN-1 (6 out of 28), highlighting potential functional differences between individual tumors in their capacity to regulate activin/TGFB signaling. Within the heterogenous nonseminomas, expression of signaling modulators was variable and reflected the degree of somatic differentiation. Thus, synthesis of activin and TGFB-signaling modulators may be affected by spermatogenic disruption and altered hormone levels in the testis.

scholarly journals Desmosomes as Signaling Hubs in the Regulation of Cell Behavior

2021 ◽  
Vol 9 ◽  
Author(s):  
Lisa Müller ◽  
Mechthild Hatzfeld ◽  
René Keil
Keyword(s):  
Signaling Pathways ◽  
Structural Properties ◽  
Posttranslational Modifications ◽  
Current Knowledge ◽  
Intercellular Junctions ◽  
Cell Behavior ◽  
Specific Expression ◽  
Tissue Integrity ◽  
Independent Functions ◽  
And Function

Desmosomes are intercellular junctions, which preserve tissue integrity during homeostatic and stress conditions. These functions rely on their unique structural properties, which enable them to respond to context-dependent signals and transmit them to change cell behavior. Desmosome composition and size vary depending on tissue specific expression and differentiation state. Their constituent proteins are highly regulated by posttranslational modifications that control their function in the desmosome itself and in addition regulate a multitude of desmosome-independent functions. This review will summarize our current knowledge how signaling pathways that control epithelial shape, polarity and function regulate desmosomes and how desmosomal proteins transduce these signals to modulate cell behavior.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

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