Leukotriene D4-induced proliferation of glomerular epithelial cells: PKC- and Na+-H+ exchanger-mediated response

1989 ◽  
Vol 257 (2) ◽  
pp. C232-C239 ◽  
Author(s):  
L. Baud ◽  
J. Perez ◽  
G. Cherqui ◽  
E. J. Cragoe ◽  
R. Ardaillou
Keyword(s):  
Epithelial Cells ◽  
Growth Effect ◽  
Thymidine Uptake ◽  
Promoting Effect ◽  
Leukotriene D4 ◽  
Glomerular Epithelial Cells ◽  
Ic50 Values ◽  
Growth Promoting ◽  
Pkc Activation

The growth-promoting effect of leukotriene D4 (LTD4) has been observed in a variety of cells, including human glomerular epithelial cells. The purpose of this study was to determine the mechanisms underlying this process. LTD4 induction of [3H]thymidine uptake in human glomerular epithelial cells was blocked by the LTD4 receptor antagonist L648,051 when added in a 50-fold excess and by pertussis toxin. Neither drug affected basal DNA synthesis. These results suggest that the LTD4-mediated signal transduction implies activation of a GTP-binding protein that is coupled to a specific receptor. The possible role of protein kinase C (PKC) activation was also studied. In the presence of the PKC inhibitor H-7 or after downregulation of PKC levels by chronic treatment with phorbol ester, stimulation of [3H]thymidine uptake by LTD4 was greatly inhibited. Moreover, treatment of the cells by LTD4 resulted in a time-dependent increase of cytosolic PKC activity, whereas addition of phorbol 12-myristate 13-acetate reduced this activity. Therefore PKC-dependent mechanisms are likely to mediate the growth-promoting effect of LTD4. Finally, three approaches were used to determine the potential role of the Na+-H+ exchanger. First, progressive removal of extracellular Na+ using N-methyl-D-glucamine+ as a substitute inhibited LTD4-induced [3H]thymidine uptake with a 50% inhibitory concentration (IC50) of 85 mM. Second, addition of amiloride reduced the LTD4 growth effect with an IC50 of 6.5 microM, whereas three amiloride analogues exhibited lower IC50 values in accordance with their greater affinity for the Na+-H+ exchanger.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Identification of Heat Shock Protein 32 (Hsp32) as a Novel Target in Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1616-1616
Author(s):  
Renata A. Meyer ◽  
Harald Herrmann ◽  
Karoline V. Gleixner ◽  
Alexander Gruze ◽  
Sabine Cerny-Reiterer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Heat Shock ◽  
Cell Lines ◽  
Functional Role ◽  
Lymphoblastic Leukemia ◽  
Molecular Target ◽  
Leukemic Cells ◽  
Thymidine Uptake ◽  
Ic50 Values

Abstract Heat shock proteins (Hsp) are increasingly employed as therapeutic targets in various solid tumors and leukemias. We have recently shown that Hsp32 is expressed in leukemic cells and serves as a survival-factor and molecular target in Ph+ chronic myeloid leukemia. In the present study, we examined the expression and functional role of Hsp32 in acute lymphoblastic leukemia (ALL). Leukemic cells were obtained from patients with Ph+ ALL (n=5) and Ph− ALL (n=5). In addition, Ph+ ALL cell lines (Z-119, BV-173, TOM-1, NALM-1) and Ph− ALL cell lines (RAJI, RAMOS, REH, BL-41) were used. As assessed by immunocytochemistry and qRT-PCR, leukemic cells were found to express the Hsp32 protein as well as Hsp32 mRNA in all patients and in all cell lines examined. The Hsp32-inductor hemin was found to promote the expression of Hsp32 in leukemic cells. To determine the functional role of Hsp32 in lymphoblasts, an siRNA against Hsp32 was applied. The siRNA-induced knock down of Hsp32 in RAJI cells was found to be associated with reduced growth and with an increase in apoptotic cells compared to a control siRNA against luciferase (p<0.05). In a next step, two pharmacologic inhibitors of Hsp32, pegylated zinc protoporphyrine (PEG-ZnPP) and styrene maleic acid-micelle-encapsulated ZnPP (SMA-ZnPP), were applied. As assessed by 3H-thymidine uptake experiments, both drugs were found to inhibit proliferation in the BCR/ABL+ cell lines Z-119, BV-173, and TOM-1, and in the BCR/ABL-negative ALL cell lines RAJI, RAMOS, REH, and BL-41. The effects of PEG-ZnPP and SMA-ZnPP were dose-dependent with IC50 values ranging between 1 and 10 μM, and were found to be associated with apoptosis as determined by microscopy as well as by flow cytometry and AnnexinV-staining. In NALM-1 cells, PEG-ZnPP and SMA-ZnPP also produced apoptosis and growth arrest, but the IC50 for SMA-ZnPP was slightly higher compared to other cell lines (20 μM). Effects of Hsp32-targeting drugs were also observed in primary leukemic cells obtained from patients with Ph+ ALL and Ph− ALL, with IC50 values ranging between 1 and 10 μM. No major differences were found when comparing results in imatinib-sensitive and imatinib-resistant patients. In drug combination experiments, Hsp32-targeting drugs were found to cooperate with imatinib and with AMN107 (nilotinib) in producing growth-inhibition and apoptosis in all Ph+ ALL cell lines tested. Furthermore, we were able to demonstrate strong cooperative antileukemic effects when applying Hsp32-targeting drugs in combination with bendamustine. Overall, these results suggest that Hsp32 may be a novel molecular target in ALL.

An Appraisal of the Role of Islamic Banking Development and Economic Growth

2020 ◽  
Vol 4 (4) ◽  
pp. 215-236
Author(s):  
Talat Hussain ◽  
Noman Arshed ◽  
Rukhsana Kalim
Keyword(s):  
Economic Growth ◽  
Resource Mobilization ◽  
Financial Inclusion ◽  
Islamic Banking ◽  
Islamic Banks ◽  
Promoting Effect ◽  
Efficient Resource ◽  
Growth Promoting ◽  
Banking Development

Literature is well-versed with the contribution of financial inclusion from the deposit and financing size and its role in economic growth. These contributions include a boost in economic transactions and efficient resource mobilization. Islamic financial system is different from conventional banking as it distributes the risk equitably and promotes fairness in dealings. It helps in the integration of business gains as a borrower of Islamic capital with the earnings of savers as depositors. This study has proposed two channels via which Islamic financial development may incur growth. First is bank financing penetration, and second is depositor financial inclusion. Based on the data of 41 full-fledged Islamic banks between 2012 and 2017, the results show that both increases in bank and depositor returns have a growth-promoting effect. This prompts the policymakers with new insights. Policymakers should increase Islamic banking penetration to different sectors and regulate for increased extraction of the depositor contribution from the banking financing activity.

Role of cell cycle molecules in the pathophysiology of glomerular epithelial cells

2002 ◽  
Vol 57 (4) ◽  
pp. 203-207 ◽  
Author(s):  
Michio Nagata ◽  
Yujing Shu ◽  
Shinsuke Tomari
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Glomerular Epithelial Cells

Cytotoxic effect of adriamycin and agarose-coupled adriamycin on glomerular epithelial cells: Role of free radicals

1991 ◽  
Vol 27 (10) ◽  
pp. 799-804 ◽  
Author(s):  
Roberta Bertelli ◽  
Fabrizio Ginevri ◽  
Rosanna Gusmano ◽  
Gian Marco Ghiggeri
Keyword(s):  
Free Radicals ◽  
Epithelial Cells ◽  
Cytotoxic Effect ◽  
Glomerular Epithelial Cells

Role of iron chelators in growth-promoting effect on mouse hybridoma cells in a chemically defined medium

1987 ◽  
Vol 23 (12) ◽  
pp. 815-820 ◽  
Author(s):  
Noritsugu Yabe ◽  
Miwa Kato ◽  
Yutaka Matsuya ◽  
Isao Yamane ◽  
Muneaki Iizuka ◽  
...  
Keyword(s):  
Defined Medium ◽  
Hybridoma Cells ◽  
Iron Chelators ◽  
Chemically Defined Medium ◽  
Promoting Effect ◽  
Growth Promoting

scholarly journals Leukotriene D4-induced mobilization of intracellular Ca2+ in epithelial cells is critically dependent on activation of the small GTP-binding protein Rho

1996 ◽  
Vol 316 (1) ◽  
pp. 239-245 ◽  
Author(s):  
Eva GRÖNROOS ◽  
Tommy ANDERSSON ◽  
Åsa SCHIPPERT ◽  
Limin ZHENG ◽  
Anita SJÖLANDER
Keyword(s):  
Epithelial Cells ◽  
G Protein ◽  
Major Effect ◽  
Rho Proteins ◽  
Extracellular Medium ◽  
Leukotriene D4 ◽  
Tyrosine Residues ◽  
Phospholipase Cγ1 ◽  
Mechanism Of Interaction

We have previously shown that the leukotriene D4 (LTD4)-induced mobilization of intracellular Ca2+ in epithelial cells is mediated by a G-protein that is distinctly different from the pertussis toxin-sensitive G-protein that regulates the subsequent influx of Ca2+. In the present study, we attempted to gain further knowledge about the mechanisms involved in the LTD4-induced mobilization of intracellular Ca2+ in epithelial cells by investigating the effects of compactin, an inhibitor of the isoprenylation pathway, on this signalling event. In cells preincubated with 10 μM compactin for 48 h, the LTD4-induced mobilization of intracellular Ca2+ was reduced by 75% in comparison with control cells. This reduction was reversed by co-administration of mevalonate (1 mM). The effect of compactin occurred regardless of whether or not Ca2+ was present in the extracellular medium, suggesting that isoprenylation must occur before Ca2+ is released from intracellular stores. In accordance with this, we also found that both the LTD4-induced formation of inositol 1,4,5-trisphosphate and the LTD4-induced phosphorylation of phospholipase Cγ1 (PLCγ1) on tyrosine residues were significantly reduced in compactin-pretreated cells. These results open up the possibility that the activation of PLCγ1 is related to a molecule that is sensitive to impaired activity of the isoprenylation pathway, such as a small monomeric G-protein. This idea was supported by the observation that Clostridium botulinum C3 exoenzyme-induced inhibition of Rho proteins abolished the LTD4-induced intracellular mobilization of Ca2+. A regulatory role of Rho proteins in the LTD4-induced activation of PLCγ1 is unlikely to be indirectly mediated via an effect on the cytoskeleton, since cytochalasin D had no major effect on the LTD4-induced mobilization of Ca2+. Although the mechanism of interaction remains to be elucidated, the present findings indicate an important role of an isoprenylated protein such as Rho in the LTD4-induced Ca2+ signal.

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