ABCA4-Associated Stargardt Disease

2020 ◽  
Vol 237 (03) ◽  
pp. 267-274 ◽  
Author(s):  
Mubeen Khan ◽  
Frans P.M. Cremers
Keyword(s):  
Autosomal Recessive ◽  
Late Onset ◽  
Human Kidney ◽  
In Vitro Assays ◽  
Kidney Cells ◽  
Stargardt Disease ◽  
Abca4 Gene ◽  
Transcriptomics Data ◽  
Degree Of Severity

AbstractAutosomal recessive Stargardt disease (STGD1) is associated with variants in the ABCA4 gene. The phenotypes range from early-onset STGD1, that clinically resembles severe cone-rod dystrophy, to intermediate STGD1 and late-onset STGD1. These different phenotypes can be correlated with different combinations of ABCA4 variants which can be classified according to their degree of severity. A significant fraction of STGD1 cases, particularly late-onset STGD1 cases, were shown to carry only a single ABCA4 variant. A frequent coding variant (p.Asn1868Ile) was recently identified which – in combination with a severe ABCA4 variant – is generally associated with late-onset STGD1. In addition, an increasing number of rare deep-intronic variants have been found and some of these are also associated with late-onset STGD1. The effect of these and other variants on ABCA4 RNA was tested using in vitro assays in human kidney cells using specially designed midigenes. With stem cells and photoreceptor progenitor cells derived from patient skin or blood cells, retina-specific splice defects can be assessed. With expert clinical examination to distinguish STGD1 cases from other maculopathies, as well as in-depth genomics and transcriptomics data, it is now possible to identify both mutant ABCA4 alleles in > 95% of cases.

scholarly journals Cytomegalovirus infection of human kidney cells in vitro

1991 ◽  
Vol 40 (5) ◽  
pp. 954-960 ◽  
Author(s):  
Jarkko A. Ustinov ◽  
Raisa J. Loginov ◽  
Pirkko M. Mattila ◽  
Virpi K. Nieminen ◽  
Jukka I. Suni ◽  
...  
Keyword(s):  
Cytomegalovirus Infection ◽  
Human Kidney ◽  
Kidney Cells

scholarly journals Congener-Specific Polychlorinated Biphenyl–Induced Cell Death in Human Kidney Cells In Vitro: Potential Role of Caspase

2006 ◽  
Vol 25 (5) ◽  
pp. 341-347 ◽  
Author(s):  
Y. Q. Chen ◽  
S. De ◽  
S. Ghosh ◽  
S. K. Dutta
Keyword(s):  
Cell Death ◽  
Proximal Tubule ◽  
Human Kidney ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Kidney Cells ◽  
Dependent Manner ◽  
Caspase Inhibitor ◽  
Pcb Congeners

Polychlorinated biphenyls (PCBs) are among the most widespread and persistent pollutants in the global environment. Coplanar and noncoplanar PCBs have been shown to cause congener-specific apoptosis mediated neurotoxicity in rats. Very few, if any, such studies have been reported on human renal cell toxicity. The authors report here caspase-dependent or caspase-independent renal toxicity, as measured by apoptotic death induced by PCBs, depending on the planarity of congeners PCB-77 (coplanar) and PCB-153 (noncoplanar) in human kidney cells (HK2) in vitro. The authors have combined morphological and biological techniques to discover the relevance of apoptosis in renal proximal tubule cell death induced by these two PCB congeners. Treatment with both PCB congeners caused accelerated apoptosis in a time-and concentration-dependent manner. Based on our findings using human kidney (HK2) cells, there was more apoptosis-mediated loss of cell viability by non– ortho-substituted PCB-77 when compared to PCB-153. A significant increase of caspase-3 expression through immunoblot studies showed the involvement of apoptosis by PCB-77 compared to none by PCB-153. The broad-spectrum caspase inhibitor z-VAD-fmk showed increased cell death when treated by PCB-153, but not by PCB-77, confirming that caspase inhibitor induced a switch in the mode of cell death. It is reasonable to assume that apoptotic cell death in the renal proximal tubule cells treated by PCBs may have both caspase-dependent and caspase-independent pathways.

scholarly journals IN VIVO AND IN VITRO EXPRESSION OF SOMATOSTATIN BY HUMAN KIDNEY CELLS. • 2213

1996 ◽  
Vol 39 ◽  
pp. 371-371
Author(s):  
Martin A Turman ◽  
M. Sue O'Dorisio ◽  
Thomas M O'Dorisio ◽  
Courtney A Apple
Keyword(s):  
Human Kidney ◽  
Kidney Cells ◽  
In Vitro Expression

scholarly journals Noggin rescues age-related stem cell loss in the brain of senescent mice with neurodegenerative pathology

2018 ◽  
Vol 115 (45) ◽  
pp. 11625-11630 ◽  
Author(s):  
María Díaz-Moreno ◽  
Tomás Armenteros ◽  
Simona Gradari ◽  
Rafael Hortigüela ◽  
Laura García-Corzo ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Late Onset ◽  
Hippocampal Neurogenesis ◽  
Bmp Signaling ◽  
In Vitro Assays ◽  
Age Related ◽  
Samp8 Mice ◽  
The Brain

Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer’s disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored. We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a nontransgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in BMP6 protein, enhanced canonical BMP signaling, and increased astroglial differentiation. In vitro assays demonstrate that BMP6 severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway and its progliogenic effect in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain’s natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.

scholarly journals CCDC66 frameshift variant associated with a new form of early-onset progressive retinal atrophy in Portuguese Water Dogs

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Leonardo Murgiano ◽  
Doreen Becker ◽  
Courtney Spector ◽  
Kendall Carlin ◽  
Evelyn Santana ◽  
...  
Keyword(s):  
Early Onset ◽  
Autosomal Recessive ◽  
Late Onset ◽  
Unrelated Control ◽  
Progressive Retinal Atrophy ◽  
Mutant Transcript ◽  
Retinal Atrophy ◽  
Portuguese Water ◽  
New Form

AbstractAberrant photoreceptor function or morphogenesis leads to blinding retinal degenerative diseases, the majority of which have a genetic aetiology. A variant in PRCD previously identified in Portuguese Water Dogs (PWDs) underlies prcd (progressive rod-cone degeneration), an autosomal recessive progressive retinal atrophy (PRA) with a late onset at 3–6 years of age or older. Herein, we have identified a new form of early-onset PRA (EOPRA) in the same breed. Pedigree analysis suggested an autosomal recessive inheritance. Four PWD full-siblings affected with EOPRA diagnosed at 2–3 years of age were genotyped (173,661 SNPs) along with 2 unaffected siblings, 2 unaffected parents, and 15 unrelated control PWDs. GWAS, linkage analysis and homozygosity mapping defined a 26-Mb candidate region in canine chromosome 20. Whole-genome sequencing in one affected dog and its obligatory carrier parents identified a 1 bp insertion (CFA20:g.33,717,704_33,717,705insT (CanFam3.1); c.2262_c.2263insA) in CCDC66 predicted to cause a frameshift and truncation (p.Val747SerfsTer8). Screening of an extended PWD population confirmed perfect co-segregation of this genetic variant with the disease. Western blot analysis of COS-1 cells transfected with recombinant mutant CCDC66 expression constructs showed the mutant transcript translated into a truncated protein. Furthermore, in vitro studies suggest that the mutant CCDC66 is mislocalized to the nucleus relative to wild type CCDC66. CCDC66 variants have been associated with inherited retinal degenerations (RDs) including canine and murine ciliopathies. As genetic variants affecting the primary cilium can cause ciliopathies in which RD may be either the sole clinical manifestation or part of a syndrome, our findings further support a role for CCDC66 in retinal function and viability, potentially through its ciliary function.

scholarly journals Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin Α5β1 Is a Modulator of Extravillous Trophoblast Functions

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1369 ◽  
Author(s):  
Rattila ◽  
Dunk ◽  
Im ◽  
Grichenko ◽  
Zhou ◽  
...  
Keyword(s):  
African American Women ◽  
Late Onset ◽  
Cell Movement ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
In Vitro Assays ◽  
The Family ◽  
Oxygen Conditions ◽  
Movement Tracking

Human pregnancy-specific glycoproteins (PSGs) serve immunomodulatory and pro-angiogenic functions during pregnancy and are mainly expressed by syncytiotrophoblast cells. While PSG mRNA expression in extravillous trophoblasts (EVTs) was reported, the proteins were not previously detected. By immunohistochemistry and immunoblotting, we show that PSGs are expressed by invasive EVTs and co-localize with integrin 5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to 51 and induces the formation of focal adhesion structures resulting in adhesion of primary EVTs and EVT-like cell lines under 21% oxygen and 1% oxygen conditions. Furthermore, we found that PSG1 can simultaneously bind to heparan sulfate in the extracellular matrix and to 51 on the cell membrane. Wound healing assays and single-cell movement tracking showed that immobilized PSG1 enhances EVT migration. Although PSG1 did not affect EVT invasion in the in vitro assays employed, we found that the serum PSG1 concentration is lower in African-American women diagnosed with early-onset and late-onset preeclampsia, a pregnancy pathology characterized by shallow trophoblast invasion, than in their respective healthy controls only when the fetus was a male; therefore, the reduced expression of this molecule should be considered in the context of preeclampsia as a potential therapy.

scholarly journals In Vitro Evaluation of a Stable Monomeric Gold(II) Complex with Hematoporphyrin IX: Cytotoxicity against Tumor and Kidney Cells, Cellular Accumulation, and Induction of Apoptosis

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Georgi Momekov ◽  
Dilyan Ferdinandov ◽  
Spiro Konstantinov ◽  
Sonja Arpadjan ◽  
Daniela Tsekova ◽  
...  
Keyword(s):  
Cell Lines ◽  
Apoptotic Cell ◽  
Human Kidney ◽  
Gold Complex ◽  
Kidney Cells ◽  
Tumor Cell Lines ◽  
Platinum Drug ◽  
Pharmacological Targets ◽  
Hematoporphyrin Ix

The antineoplastic potential of a stable monomeric Au(II) complex with hematoporphyrin IX (Hp), namely [Au(II)Hp-2H.(H2O)2], was investigated in a panel of tumor cell lines. The complex exhibits strong cytotoxicity, whereby the leukaemia- and lymphoma-derived cell lines are more sensitive, withIC50values comparable to those of the reference anticancer drug cisplatin. In contrast, the solid tumor models are more sensitive to the platinum drug. A comparative assessment of both agents against the human kidney cell line 293T has shown that [Au(II)Hp-2H.(H2O)2] is less cytotoxic. The gold complex induces oligonucleosomal DNA fragmentation in tumour cells following 24-hour treatment and hence its cytotoxic effect is at least partly mediated by induction of apoptotic cell death. A prominent intracellular gold accumulation was detected after treating tumor cells with [Au(II)Hp-2H.(H2O)2] which shows that its putative pharmacological targets are readily accessible after a short incubation period.

Melatonin pretreatment of human adipose tissue-derived mesenchymal stromal cells enhances their prosurvival and protective effects on human kidney cells

2015 ◽  
Vol 308 (12) ◽  
pp. F1474-F1483 ◽  
Author(s):  
Jing Zhao ◽  
Yoon Kow Young ◽  
Julie Fradette ◽  
Nicoletta Eliopoulos
Keyword(s):  
Adipose Tissue ◽  
Cell Therapy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Injury ◽  
Human Kidney ◽  
Great Promise ◽  
Kidney Cells ◽  
Protective Effects

The efficacy of cell therapy for many diseases can be limited by the poor survival of implanted cells in an environment of tissue injury. Melatonin has been reported to have antioxidative and antiapoptotic effects. Adipose tissue-derived mesenchymal stromal cells (ASCs), cells easily obtained in high amounts and with minimal discomfort, have shown great promise in cell therapy applications, such as in acute kidney injury. We hypothesized that melatonin pretreatment of human ASCs (hASCs) would improve their renoprotective and prosurvival effects. We therefore investigated the action of melatonin on hASCs, as well as the effect of the resulting hASCs-conditioned media (CM) on human kidney cells exposed to oxidative and apoptotic injury-provoking doses of cisplatin. Our results demonstrated that pretreatment of hASCs with melatonin, 100 μM for 3 h, significantly increased their proliferation and their expression of prosurvival P-Erk1/2 and P-Akt, and of antioxidative enzymes catalase and heme oxygenase (HO)-1. In addition, the CM from hASCs pretreated with melatonin provoked a significantly higher proliferation and migration of HK-2 human kidney epithelial cells. Furthermore, this CM exerted significantly higher prosurvival and antiapoptotic actions on HK-2 cells exposed to cisplatin in vitro. Western blot analysis showed higher expression of P-Erk1/2, Bcl-2, SOD-1, and HO-1 in the HK-2 cells exposed to cisplatin in the presence of CM from melatonin-pretreated hASCs. In sum, our study revealed that in vitro pretreatment of hASCs with melatonin may significantly enhance their survival and their therapeutic effectiveness on injured tissue.

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