Heterotrimeric G-Proteins Are Implicated in the Regulation of Apoptosis in Pancreatic β-Cells

Loweth, Anne C.; Williams, Gwyn T.; Scarpello, J. H. B.; Morgan, Noel G.

doi:10.1006/excr.1996.0344

Cited by 43 publications

(44 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although MSR may scavenge cytotoxic ligands produced endogenously by the cells exposed to fluoride anions, the The global activation of the heterotrimers of membranebound G-proteins has been reported as a potential mechanism underlying induction of apoptosis by fluoride anions. 27,28,37 It has been known for several decades that fluoride anions can react with aluminium ions forming AlFx complexes that mimic the gamma phosphate of a GTP and thereby activate cellular GTP-binding proteins. 38 Fluoride anions may form a complex with a trace of aluminium ions from glassware, which can activate G-proteins.…”

Section: Discussionmentioning

confidence: 99%

“…27 The proapoptotic effect of fluoride anions is thought to operate through a signaling transduction system composed of the heterotrimers of G-proteins in the cellular membrane. 28 We therefore examined whether stimulation with NaF triggers apoptosis of human THP-1 monocytic cells. Cell viability was determined by staining with a combination of the DNA-binding fluorochromes acridine orange and ethidium bromide.…”

Section: Induction Of Apoptosis By Activation Of G-proteins With Fluomentioning

confidence: 99%

“…27 The apoptosis-promoting effect of fluoride anions may occur through activation of heterotrimeric Gproteins. 28 The different susceptibility to apoptosis between monocytes and macrophages points to the possibility that certain molecules associated with macrophage differentiation may regulate apoptosis of macrophages. MSR expression represents a late-stage marker of monocyte-macrophage differentiation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

De novo expression of the class-A macrophage scavenger receptor conferring resistance to apoptosis in differentiated human THP-1 monocytic cells

et al. 1999

View full text Add to dashboard Cite

The class-A macrophage scavenger receptor (MSR) is a trimeric multifunctional protein expressed selectively in differentiated monomyeloid phagocytes which mediates uptake of chemically modified lipoproteins and bacterial products. This study investigated whether MSR plays a role in the regulation of apoptosis, a model of genetically programmed cell death. De novo expression of MSR occurred in human THP-1 monocytic cells differentiated with phorbol esters, which activated a nuclear transcription factor binding to the Ap1/ets-like domain of the MSR promoter. The phorbol ester-stimulated THP-1 cells also expressed increased levels of the pro-apoptotic gene products, caspase-3 and Fas ligand, but the cells exhibited no change in apoptosis. Global activation of GTP-binding proteins with fluoride anions triggered apoptosis of THP-1 cells in a time-and concentration-dependent manner, demonstrated by nuclear shrinkage and fragmentation and internucleosomal DNA fragmentation. However, the MSR-expressing THP-1 macrophage-like cells showed a significant reduction in apoptosis compared to undifferentiated control THP-1 cells, which produce MSR at undetectable levels. Fluoride stimulation also triggered apoptosis of human Jurkat T cells. Stimulation with phorbol ester made no difference in apoptosis between treated and untreated Jurkat cells. Finally, Chinese hamster ovary (CHO) cells overexpressing the class-A MSR type I by cDNA transfection showed markedly increased resistance to Gprotein-coupled apoptosis. Thus, de novo expression of MSR associated with monocyte maturation into macrophages appears to confer the resistance of macrophages to apoptotic stimulation by G-protein activation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Induction Of Apoptosis By Activation Of G-proteins With Fluomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

De novo expression of the class-A macrophage scavenger receptor conferring resistance to apoptosis in differentiated human THP-1 monocytic cells

et al. 1999

View full text Add to dashboard Cite

show abstract

“…However, this can be difficult using primary human islets of Langerhans since the tissue is normally available in only limited quantity and quantitation of -cell apoptosis is hampered by the spatial organisation of the endocrine cells within the islet structure and by the presence of other cell types. For these reasons, many workers have chosen to use cultured rodent -cell lines as model systems for the study of the control of apoptosis (Loweth et al 1996a, Di Matteo et al 1997, Bai et al 1999, Nakata et al 1999, Olejnicka et al 1999, Tejedo et al 1999, Ahmad et al 2000, Ammendrup et al 2000, Bonny et al 2000, Krautheim et al 2000, Sjoholm et al 2000, Baker et al 2001. The implicit assumption in such studies is that the responses observed are relevant to the aetiology of diabetes and that the cell lines respond in a similar manner to normal human islets of Langerhans.…”

Section: Introductionmentioning

confidence: 99%

“…In previous studies, we have employed RIN5mF cells to investigate the role of heterotrimeric G-protein-dependent pathways in the control of -cell apoptosis and have shown that these cells express an anti-apoptotic pathway that is under the control of a pertussis toxin (Ptx)-sensitive G-protein (Loweth et al 1996a, Elliott et al 2001. A similar pathway also exists in normal rat islets (Loweth et al 1996a) suggesting that, at least in this respect, RINm5F cells are an appropriate model system. However, it is not known whether this mechanism is operative in human islet cells.…”

Section: Introductionmentioning

confidence: 99%

Differential effects of genistein on apoptosis induced by fluoride and pertussis toxin in human and rat pancreatic islets and RINm5F cells

Elliott¹,

Scarpello²,

Morgan³

2002

Journal of Endocrinology

View full text Add to dashboard Cite

Clonal pancreatic -cell lines have been used widely for the study of the factors involved in the regulation of apoptosis but it has not been firmly established that the response of normal islets mirrors that found in transformed -cells. In the present work, the role of pertussis toxin (Ptx)-sensitive G-proteins in the control of -cell apoptosis was studied in isolated rat and human islets of Langerhans and compared with the clonal -cell line, RINm5F. Annexin-V and deoxycarboxyfluoroscein diacetate staining was used to identify viable, apoptotic and necrotic cells directly, under fluorescence illumination. Treatment of human and rat islet cells with the G-protein activator fluoride (NaF; 5 mM) caused a marked increase in apoptosis that was further potentiated in islets pretreated with Ptx. The tyrosine kinase inhibitor genistein (100 µM) also increased islet cell apoptosis and the combination of 100 µM genistein and 5 mM NaF did not lead to any diminution of the apoptotic response. This latter effect was quite different from that seen in RINm5F cells where the combination of 100 µM genistein and 5 mM NaF resulted in much less apoptosis than was observed with either agent alone. In islets treated with a lower concentration of genistein (25 µM; that did not, itself, increase cell death), the drug attenuated NaF-induced apoptosis and also blocked the enhancement mediated by Ptx. These results revealed that human (and rat) islets are equipped with a Ptx-sensitive pathway that may be regulated by tyrosine phosphorylation and is anti-apoptotic. However, they also define conditions under which marked differences in response between RINm5F cells and normal islets were observed and they suggest that care should be taken when extrapolating data obtained with clonal cell lines to the situation in normal islet cells.

show abstract

ER‐resident G_i2 protein controls sar1 translocation onto the ER during budding of transport vesicles

Nakagawa

Umadome

Miyazaki

et al. 2011

J of Cellular Biochemistry

View full text Add to dashboard Cite

In our previous study, fluoride ([AlF(4) ](-) ) disturbed ER-to-Golgi transport through the activation of ER-resident heterotrimeric G protein (ER-G protein). Therefore, ER-G protein may be implicated in ER-to-Golgi transport at the early stage prior to coat protein assembly. Sar1 translocation onto the endoplasmic reticulum (ER) membrane is suppressed by non-selective protein kinase inhibitor H89, suggesting the participation of H89-sensitive kinase in this process. To investigate the involvement of ER-G protein in ER-to-Golgi transport, the effect of G(i) protein activator (mastoparan 7) was examined on Sar1 translocation onto the ER in a cell-free system consisting of microsome membrane and cytosol. Sar1 translocation onto the microsome membrane was induced by addition of GTPγS in the cell-free system. Translocation of Sar1 by GTPγS was suppressed significantly by both H89 and mastoparan 7. Mastoparan 7 suppressed the translocation of Sar1 onto the microsome membrane with dosage dependency, but mastoparan 17, the inactive analog of mastoparan 7, had no effect on Sar1 translocation. The suppressive effect of mastoparan 7 was recovered by treatment with pertussis toxin (IAP). Moreover, G(i2) protein was detected on the microsome membrane by western blotting for heterotrimeric G(i) proteins. These results indicate that ER-G(i2) protein modulated Sar1 translocation onto the ER, suggesting that ER-resident G(i2) protein is an important negative regulator of vesicular transport at the early stage of vesicle formation before coat protein assembly on the ER.

show abstract

Heterotrimeric G-Proteins Are Implicated in the Regulation of Apoptosis in Pancreatic β-Cells

Cited by 43 publications

References 0 publications

De novo expression of the class-A macrophage scavenger receptor conferring resistance to apoptosis in differentiated human THP-1 monocytic cells

De novo expression of the class-A macrophage scavenger receptor conferring resistance to apoptosis in differentiated human THP-1 monocytic cells

Differential effects of genistein on apoptosis induced by fluoride and pertussis toxin in human and rat pancreatic islets and RINm5F cells

ER‐resident G_i2 protein controls sar1 translocation onto the ER during budding of transport vesicles

Contact Info

Product

Resources

About

Heterotrimeric G-Proteins Are Implicated in the Regulation of Apoptosis in Pancreatic β-Cells

Cited by 43 publications

References 0 publications

De novo expression of the class-A macrophage scavenger receptor conferring resistance to apoptosis in differentiated human THP-1 monocytic cells

De novo expression of the class-A macrophage scavenger receptor conferring resistance to apoptosis in differentiated human THP-1 monocytic cells

Differential effects of genistein on apoptosis induced by fluoride and pertussis toxin in human and rat pancreatic islets and RINm5F cells

ER‐resident Gi2 protein controls sar1 translocation onto the ER during budding of transport vesicles

Contact Info

Product

Resources

About

ER‐resident G_i2 protein controls sar1 translocation onto the ER during budding of transport vesicles