Glycosphingolipids and plasma lipoproteins: a review

1984 ◽  
Vol 62 (6) ◽  
pp. 385-397 ◽  
Author(s):  
Subroto Chatterjee ◽  
Peter O. Kwiterovich Jr.
Keyword(s):  
Human Fibroblasts ◽  
Ldl Receptor ◽  
Plasma Lipoproteins ◽  
In Vivo Model ◽  
Renal Tubular Cells ◽  
Cultured Human Fibroblasts ◽  
Vitro Model ◽  
Renal Tubular

Glycosphingolipids (GSL) are complex, sugar-containing lipids that are transported in plasma on lipoproteins, particularly low density (beta) lipoproteins (LDL). LDL are taken up and metabolized by cells through a LDL receptor-mediated pathway. Cells from receptor-negative familial hypercholesterolemic (FH) homozygotes lack a functional LDL receptor and the cellular uptake of LDL occurs through a LDL receptor-independent pathway. We have studied the relation between LDL and GSL metabolism using an in vitro model of cultured human fibroblasts and an in vivo model of renal tubular cells shed in the urine. Using biochemical, morphological, and immunocytological techniques, we have demonstrated that LDL taken up through the LDL receptor-independent pathway results in the accumulation of GSL in cells in vitro and in vivo. The storage of GSL is localized to intracytoplasmic vesicles and such storage can be modulated by changing the concentration of LDL in the culture medium or in plasma. The possible effect of LDL on certain steps in the intracellular metabolism of GSL in normal and receptor-negative homozygous FH cells is reviewed.

scholarly journals Radiofrequency Irradiation Modulates TRPV1-Related Burning Sensation in Rosacea

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1424
Author(s):  
Seyeon Oh ◽  
Myeongjoo Son ◽  
Joonhong Park ◽  
Donghwan Kang ◽  
Kyunghee Byun
Keyword(s):  
Burning Sensation ◽  
In Vivo Model ◽  
Molecular Evidence ◽  
Exposed Skin ◽  
Heat Treated ◽  
Vitro Model ◽  
Effective Use ◽  
Inflammatory Molecules

Rosacea is a skin inflammatory condition that is accompanied by not only redness and flushing but also unseen symptoms, such as burning, stinging, and itching. TRPV1 expression in UVB-exposed skin can lead to a painful burning sensation. Upregulated TRPV1 expression helps release neuropeptides, including calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide, which can activate macrophage and inflammatory molecules. In this study, we found that radiofrequency (RF) irradiation reduced TRPV1 activation and neuropeptide expression in a UVB-exposed in vivo model and UVB- or heat-treated in an in vitro model. RF irradiation attenuated neuropeptide-induced macrophage activation and inflammatory molecule expression. Interestingly, the burning sensation in the skin of UVB-exposed mice and patients with rosacea was significantly decreased by RF irradiation. These results can provide experimental and molecular evidence on the effective use of RF irradiation for the burning sensation in patients with rosacea.

scholarly journals Astrogliosis in an Experimental Model of Hypovitaminosis B12: A Cellular Basis of Neurological Disorders due to Cobalamin Deficiency

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2261
Author(s):  
Zuzanna Rzepka ◽  
Jakub Rok ◽  
Justyna Kowalska ◽  
Klaudia Banach ◽  
Justyna Magdalena Hermanowicz ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Cobalamin Deficiency ◽  
Confocal Laser ◽  
In Vivo Model ◽  
Cellular Expression ◽  
Wide Range ◽  
Vitro Model

Cobalamin deficiency affects human physiology with sequelae ranging from mild fatigue to severe neuropsychiatric abnormalities. The cellular and molecular aspects of the nervous system disorders associated with hypovitaminosis B12 remain largely unknown. Growing evidence indicates that astrogliosis is an underlying component of a wide range of neuropathologies. Previously, we developed an in vitro model of cobalamin deficiency in normal human astrocytes (NHA) by culturing the cells with c-lactam of hydroxycobalamin (c-lactam OH-Cbl). We revealed a non-apoptotic activation of caspases (3/7, 8, 9) in cobalamin-deficient NHA, which may suggest astrogliosis. The aim of the current study was to experimentally verify this hypothesis. We indicated an increase in the cellular expression of two astrogliosis markers: glial fibrillary acidic protein and vimentin in cobalamin-deficient NHA using Western blot analysis and immunocytochemistry with confocal laser scanning microscopy. In the next step of the study, we revealed c-lactam OH-Cbl as a potential non-toxic vitamin B12 antagonist in an in vivo model using zebrafish embryos. We believe that the presented results will contribute to a better understanding of the cellular mechanism underlying neurologic pathology due to cobalamin deficiency and will serve as a foundation for further studies.

scholarly journals Evaluation In Vivo and In Vitro of the Antioxidant, Antinociceptive, and Anti-Inflammatory Activities of Biflavonoids From Ouratea hexasperma and O. ferruginea

2019 ◽  
Vol 14 (6) ◽  
pp. 1934578X1985680 ◽  
Author(s):  
Poliana de Araujo Oliveira ◽  
Queli Cristina Fidelis ◽  
Thayane Ferreira da Costa Fernandes ◽  
Milene Conceição de Souza ◽  
Dayane Magalhães Coutinho ◽  
...  
Keyword(s):  
Type I Collagen ◽  
In Vivo Model ◽  
Type I ◽  
Anti Inflammatory ◽  
Vitro Model ◽  
Factor Α ◽  
Necrosis Factor

Ouratea species are used for the treatment of inflammation-related diseases such as rheumatism and arthritic disorders. The Ouratea genus is a rich source of flavonoids and bioflavonoids and for this reason we evaluated the effects of the biflavonoid fractions from the leaves of O. hexasperma (OHME) and O. ferruginea (OFME) in the in vivo model of complete Freund’s adjuvant (CFA)-induced arthritis and in the in vitro model of oxidative stress and cellular viability. The CFA-induced arthritis model in rats was followed by paw volume, articular incapacitation and Randall-selitto models, as well as quantification of cytokines and serum C-terminal telopeptide of type I collagen levels. OHME and OFME demonstrated antinociceptive and anti-inflammatory activities, as well as improvement in articular incapacity and reduction in levels of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α, and type 1 collagen, and increased cell viability. No adverse effects were observed. The results suggest that OHME and OFME can reduce inflammation and bone resorption besides their antioxidant action.

scholarly journals Differential Effects of Platelets Selectively Activated by Protease-Activated Receptors on Meniscal Cells

2019 ◽  
Vol 48 (1) ◽  
pp. 197-209 ◽  
Author(s):  
Hongyao Xu ◽  
Xiangjie Zou ◽  
Pengcheng Xia ◽  
Mohammad Ahmad Kamal Aboudi ◽  
Ran Chen ◽  
...  
Keyword(s):  
In Vivo Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protease Activated Receptors ◽  
Activated Platelets ◽  
Meniscal Tissue ◽  
Vitro Model ◽  
High Level ◽  
Meniscal Cells

Background: Meniscal injury is very common, and injured meniscal tissue has a limited healing ability because of poor vascularity. Platelets contain both pro- and anti-angiogenic factors, which can be released by platelet selective activation. Hypothesis: Platelets release a high level of vascular endothelial growth factor (VEGF) when they are activated by protease-activated receptor 1 (PAR1), whereas the platelets release endostatin when they are activated by protease-activated receptor 4 (PAR4). The PAR1-treated platelets enhance the proliferation of meniscal cells in vitro and promote in vivo healing of wounded meniscal tissue. Study Design: Controlled laboratory study. Method: Platelets were isolated from human blood and activated with different reagents. The released growth factors from the activated platelets were determined by immunostaining and enzyme-linked immunosorbent assay. The effects of the platelets with different treatments on meniscal cells were tested by an in vitro model of cell culture and an in vivo model of wounded meniscal healing. Results: The results indicated that platelets contained both pro- and antiangiogenic factors including VEGF and endostatin. In unactivated platelets, VEGF and endostatin were contained inside of the platelets. Both VEGF and endostatin were released from the platelets when they were activated by thrombin. However, only VEGF was released from the platelets when they were activated by PAR1, and only endostatin was released from the platelets when they were activated by PAR4. The rat meniscal cells grew much faster in the medium that contained PAR1-activated platelets than in the medium that contained either PAR4-activated platelets or unactivated platelets. The wounds treated with PAR1-activated platelets healed faster than those treated with either PAR4-activated platelets or unactivated platelets. Many blood vessel–like structures were found in the wounded menisci treated with PAR1-activated platelets. Conclusion: The PAR1-activated platelets released high levels of VEGF, which increased the proliferation of rat meniscal cells in vitro, enhanced the vascularization of menisci in vivo, and promoted healing of wounded menisci. Clinical Relevance: Our results suggested that selective activated platelets can be used clinically to enhance healing of wounded meniscal tissue.

scholarly journals Glucosamine Enhancement of BDNF Expression and Animal Cognitive Function

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3667
Author(s):  
Lien-Yu Chou ◽  
Yu-Ming Chao ◽  
Yen-Chun Peng ◽  
Hui-Ching Lin ◽  
Yuh-Lin Wu
Keyword(s):  
Cognitive Function ◽  
In Vivo Model ◽  
Mrna Levels ◽  
Bdnf Expression ◽  
Object Recognition Test ◽  
Creb Phosphorylation ◽  
Downstream Signaling ◽  
Vitro Model

Brain-derived neurotrophic factor (BDNF) is an important factor for memory consolidation and cognitive function. Protein kinase A (PKA) signaling interacts significantly with BDNF-provoked downstream signaling. Glucosamine (GLN), a common dietary supplement, has been demonstrated to perform a variety of beneficial physiological functions. In the current study, an in vivo model of 7-week-old C57BL/6 mice receiving daily intraperitoneal injection of GLN (0, 3, 10 and 30 mg/animal) was subjected to the novel object recognition test in order to determine cognitive performance. GLN significantly increased cognitive function. In the hippocampus GLN elevated tissue cAMP concentrations and CREB phosphorylation, and upregulated the expression of BDNF, CREB5 and the BDNF receptor TrkB, but it reduced PDE4B expression. With the in vitro model in the HT22 hippocampal cell line, GLN exposure significantly increased protein and mRNA levels of BDNF and CREB5 and induced cAMP responsive element (CRE) reporter activity; the GLN-mediated BDNF expression and CRE reporter induction were suppressed by PKA inhibitor H89. Our current findings suggest that GLN can exert a cognition-enhancing function and this may act at least in part by upregulating the BDNF levels via a cAMP/PKA/CREB-dependent pathway.

scholarly journals Mechanical loading regulates expression of talin and its mRNA, which are concentrated at myotendinous junctions

1998 ◽  
Vol 275 (3) ◽  
pp. C818-C825 ◽  
Author(s):  
Jérôme Frenette ◽  
James G. Tidball
Keyword(s):  
Mechanical Loading ◽  
In Vivo Model ◽  
Proteolytic Fragment ◽  
In Vivo Models ◽  
Hindlimb Muscles ◽  
Vitro Model ◽  
Model C ◽  
Myotendinous Junctions

The hypothesis that mechanical loading regulates talin expression in developing and adult muscle was tested using in vitro and in vivo models. Talin was selected for study because it is a key structural link between the cytoskeleton and cell membrane. In the in vitro model, C2C12myotubes were subjected to cyclic strains for 48 h. In the in vivo model, rat hindlimb muscles were unloaded for 10 days, then reloaded for 2 days. Cyclic loading of myotubes resulted in significant increases in the quantity of talin (68%) and its 190-kDa proteolytic fragment (70%), as well as talin mRNA (180%), relative to unloaded myotube cultures. Similarly, talin concentration and its mRNA increased by 68 and 136%, respectively, in soleus muscles reloaded for 2 days relative to ambulatory controls. Immunohistochemistry and in situ RT-PCR showed that talin and its mRNA are concentrated and colocalized at myotendinous junctions. Thus these findings indicate that increased mechanical loading promotes talin synthesis, which occurs principally at myotendinous junctions, according to talin mRNA distribution.

scholarly journals Increasing cGMP-dependent protein kinase I activity attenuates cisplatin-induced kidney injury through protection of mitochondria function

2013 ◽  
Vol 305 (6) ◽  
pp. F881-F890 ◽  
Author(s):  
Hasiyeti Maimaitiyiming ◽  
Yanzhang Li ◽  
Wenpeng Cui ◽  
Xiaopeng Tong ◽  
Heather Norman ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tubular Damage ◽  
Dependent Protein Kinase ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Renal Tubular

Cisplatin is widely used to treat malignancies. However, its major limitation is the development of dose-dependent nephrotoxicity. The precise mechanisms of cisplatin-induced kidney damage remain unclear, and the renoprotective agents during cisplatin treatment are still lacking. Here, we demonstrated that the expression and activity of cGMP-dependent protein kinase-I (PKG-I) were reduced in cisplatin-treated renal tubular cells in vitro as well as in the kidney tissues from cisplatin-treated mice in vivo. Increasing PKG activity by both pharmacological and genetic approaches attenuated cisplatin-induced kidney cell apoptosis in vitro. This was accompanied by decreased Bax/Bcl2 ratio, caspase 3 activity, and cytochrome c release. Cisplatin-induced mitochondria membrane potential loss in the tubular cells was also prevented by increased PKG activity. All of these data suggest a protective effect of PKG on mitochondria function in renal tubular cells. Importantly, increasing PKG activity pharmacologically or genetically diminished cisplatin-induced tubular damage and preserved renal function during cisplatin treatment in vivo. Mitochondria structural and functional damage in the kidney from cisplatin-treated mice was inhibited by increased PKG activity. In addition, increasing PKG activity enhanced ciaplatin-induced cell death in several cancer cell lines. Taken together, these results suggest that increasing PKG activity may be a novel option for renoprotection during cisplatin-based chemotherapy.

scholarly journals The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity

2019 ◽  
Vol 20 (20) ◽  
pp. 5238 ◽  
Author(s):  
Daniela Maria Tanase ◽  
Evelina Maria Gosav ◽  
Smaranda Radu ◽  
Claudia Florida Costea ◽  
Manuela Ciocoiu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
In Vivo Studies ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Induced Apoptosis ◽  
Kidney Injury Molecule 1

Acute kidney injury (AKI) following platinum-based chemotherapeutics is a frequently reported serious side-effect. However, there are no approved biomarkers that can properly identify proximal tubular injury while routine assessments such as serum creatinine lack sensitivity. Kidney-injury-molecule 1 (KIM-1) is showing promise in identifying cisplatin-induced renal injury both in vitro and in vivo studies. In this review, we focus on describing the mechanisms of renal tubular cells cisplatin-induced apoptosis, the associated inflammatory response and oxidative stress and the role of KIM-1 as a possible biomarker used to predict cisplatin associated AKI.

scholarly journals Nifedipine Upregulates ATF6-α, Caspases -12, -3, and -7 Implicating Lipotoxicity-Associated Renal ER Stress

2020 ◽  
Vol 21 (9) ◽  
pp. 3147
Author(s):  
Chiung-Chi Peng ◽  
Chang-Rong Chen ◽  
Chang-Yu Chen ◽  
Yen-Chung Lin ◽  
Kuan-Chou Chen ◽  
...  
Keyword(s):  
Er Stress ◽  
Nile Red ◽  
In Vivo Models ◽  
Beneficial Effects ◽  
Homologous Protein ◽  
Renal Tubular Cells ◽  
Activating Transcription Factor ◽  
Renal Tubular

Nifedipine (NF) is reported to have many beneficial effects in antihypertensive therapy. Recently, we found that NF induced lipid accumulation in renal tubular cells. Palmitic acid-induced renal lipotoxicity was found to be partially mediated by endoplasmic reticular (ER) stress, while it can also be elicited by NF in kidney cells; we examined the induction of suspected pathways in both in vitro and in vivo models. NRK52E cells cultured in high-glucose medium were treated with NF (30 µM) for 24–48 h. ER stress-induced lipotoxicity was explored by staining with thioflavin T and Nile red, transmission electron microscopy, terminal uridine nick-end labeling, and Western blotting. ER stress was also investigated in rats with induced chronic kidney disease (CKD) fed NF for four weeks. NF induced the production of unfolded protein aggregates, resulting in ER stress, as evidenced by the upregulation of glucose-regulated protein, 78 kDa (GRP78), activating transcription factor 6α (ATF6α), C/EBP-homologous protein (CHOP), and caspases-12, -3, and -7. In vitro early apoptosis was more predominant than late apoptosis. Most importantly, ATF6α was confirmed to play a unique role in NF-induced ER stress in both models. CKD patients with hypertension should not undergo NF therapy. In cases where it is required, alleviation of ER stress should be considered to avoid further damaging the kidneys.

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