Multiple polyphosphoinositide pathways regulate apoptotic signalling in a dorsal root ganglion derived cell line

Goswami, Rajendra; Dawson, S.A.; Dawson, Glyn

doi:10.1002/(sici)1097-4547(20000101)59:1<136::aid-jnr16>3.0.co;2-f

Cited by 19 publications

(5 citation statements)

References 44 publications

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“…Dynorphin itself has paradoxical effects, enhancing survival of mouse spinal cord neurons through opioid specific actions while promoting excitotoxic loss through nonopioid (glutamatergic) pathways (Hauser et al, 1999). Although we believe that κ‐opioids enhance OL survival by direct effects at κ‐receptors, opioids might act synergistically with other factors to affect survival as described in other cell types (Dawson et al, 1997; Goswami et al, 1998, 2000; Maneckjee and Minna, 1994).…”

Section: Discussionmentioning

confidence: 81%

Vesicle-associated membrane protein isoforms in the tiger salamander retina

2001

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Vesicle associated membrane protein (VAMP; also known as synaptobrevin) is a key component of the core complex needed for docking and fusion of synaptic vesicles with the presynaptic plasma membrane. Recent work indicates that the precise complement of presynaptic proteins associated with transmitter release and their isoforms vary among synapses, presumably conferring specific functional release properties. The retina contains two types of vesicular synapses with distinct morphologic, functional, and biochemical characteristics: ribbon and conventional synapses. Although the precise complement of presynaptic proteins is known to differ between conventional and ribbon synapses and among conventional synapses, the distribution of VAMP isoforms among retinal synapses has not been determined. The expression and localization of VAMP isoforms in the salamander retina, a major model system for studies of retinal circuitry, was examined by using immunocytochemical and immunoblotting methods. Both methods indicated that at least two VAMP isoforms were expressed in salamander retina. One isoform, recognized by an immunoglobulin M antibody that recognizes both mammalian VAMP-1 and VAMP-2, was associated with photoreceptor and bipolar cell terminals as well as many conventional synapses, and probably corresponds to mammalian VAMP-2. A different VAMP isoform associated with a subset of amacrine cells, was recognized only by antibodies directed against the N-terminus of mammalian VAMP-2. An antiserum directed against the N-terminus of mammalian VAMP-1 did not specifically recognize any salamander VAMPs in either immunocytochemical or immunoblotting experiments. Heterogeneous distribution of VAMP isoforms among conventional retinal synapses was confirmed by double labeling for synapsin I, a marker for conventional synapses. These studies indicate that VAMP isoforms are expressed heterogeneously among retinal synapses but cannot account for the differences in transmitter release characteristics at ribbon and conventional synapses. These results also corroborate previous studies in Xenopus indicating that the N-terminus of nonmammalian VAMP isoforms differs from their mammalian counterparts.

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Section: Discussionmentioning

confidence: 81%

Vesicle-associated membrane protein isoforms in the tiger salamander retina

2001

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“…10 It has been demonstrated that Akt plays an important role in the cell survival since inhibition of propidium iodide 3-kinase/Akt stimulates caspase activity and leads to apoptosis in a variety of cells. [24][25][26] Moreover, phosphorylation of Akt is reported to upregulate the expression of Bcl-2 through phosphorylation of CREB. 27,28 In the present study, IGF-1 enhanced not only the pAktlike immunoreactivity but also the pCREB-like immunoreactivity in LLC-PK 1 cells.…”

Section: Discussionmentioning

confidence: 99%

Involvement of de novo ceramide synthesis in radiocontrast-induced renal tubular cell injury

Itoh

Yano

Sendo

et al. 2006

Kidney International

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We reported previously that various radiocontrast media cause apoptosis in porcine proximal tubular (LLC-PK(1)) cells, in which reduction in B-cell lymphoma (Bcl)-2 expression and caspase-3 activation are implicated. In the present study, we investigated a role for ceramide in radiocontrast media-induced apoptosis in renal tubular cells. LLC-PK(1) cells were exposed to radiocontrast media for 30 min, followed by incubation for 24 h in normal medium. Cell viability was assessed by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt assay, while apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling stain. Immunofluorescent stains were performed using antibodies against phosphorylated Akt (pAkt) and cAMP response element binding protein (CREB) (pCREB), and ceramide. The mRNA expression and protein content of Bcl-2 were determined by reverse transcriptase-polymerase chain reaction and enzyme immunoassay, respectively. In vivo model of contrast-induced renal injury was induced in mice with unilateral renal occlusion. The cell injury induced by the nonionic radiocontrast medium ioversol was reversed by inhibiting de novo ceramide synthesis with fumonisin B(1) (FB(1)) and L-cycloserine, but not by suppressing sphingomyelin breakdown with D609. FB(1) reversed ioversol-induced decrease in the immunoreactivities of pAkt and pCREB, reduction in Bcl-2 expression and caspase-3 activation. Like ioversol, C2 ceramide and the Akt inhibitor Src homology-6 induced apoptosis by reducing pAkt and pCREB-like immunoreactivities, lowering Bcl-2 expression and enhancing caspase-3 activity. Indeed, various radiocontrast media, excluding iodixanol which showed the least nephrotoxicity, enhanced ceramide-like immunoreactivity. The role for de novo ceramide synthesis was also shown in the in vivo model of radiocontrast nephropathy. We demonstrated here for the first time that the enhancement of de novo ceramide synthesis contributes to radiocontrast nephropathy.

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“…Although the ability of the Group I mGluR subtypes to prevent the activation of caspase 1-like and caspase 3-like proteases require further investigation, one possible mechanism is suggested through phospholipase C. Group I mGluR subtypes stimulate phospholipase C and phosphoinositide hydrolysis with the subsequent activation of adenylate cyclase (Maiese et al, 1996). A decrease in phosphoinositide hydrolysis and cAMP levels in neurons has been shown to result in the activation of caspase 3 (Goswami et al, 2000). In contrast to group I mGluR activation, the individual activation of Group II or Group III mGluR subtypes did not alter the induction of either caspase 1-like or caspase 3-like proteases during NO toxicity.…”

Section: Discussionmentioning

confidence: 99%