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131.
David B. Rivers M. Paulina Dani Elaine H. Richards 《Archives of insect biochemistry and physiology》2009,71(3):173-190
The endoparasitoid Pimpla hypochondriaca injects venom during oviposition to condition its lepidopteran hosts. Venom is a complex mixture of proteins and polypeptides, many of which have been identified as enzymes, including phenoloxidase, endopeptidase, aminopeptidase, hydrolase, and angiotensin‐converting enzyme. Constituents of the venom have been shown to possess cytolytic and paralytic activity, but the modes of action of factor(s) responsible for exerting such effects have not been deciphered. In this study, we examined the mode of action of isolated venom using cultured cells (BTI‐TN‐5B1‐4). A series of blockage and inhibition assays were performed using a potent inhibitor (phenylthiourea, PTU) of venom phenoloxidase, and anti‐calreticulin antibodies. Monolayers exposed to venom alone were highly susceptible with more than 84.6±2.3% dead within 15 min. Susceptible cells displayed a retraction of cytoplasmic extensions, rounding, and swelling prior to lysis in more than half (55.7±1.7%) of the dying cells. Within 15 min of exposure to venom, cells displayed qualitative increases in [Ca+2]i as evidenced by staining with the calcium‐sensitive probe fluo‐4 AM, and mitochondrial membrane potential (ΔΨm) was undetectable by 5 min post‐treatment with venom. These venom‐mediated changes occurred regardless of whether an external source of calcium was present, or whether venom was pre‐treated with PTU. In contrast, venom toxicity was attenuated by treatment with anti‐calreticulin antibodies. Not only did fewer cells die when exposed to antibody‐treated venom but also cell swelling diminished and no increases in intracellular calcium were detected. A possible mode of action for the venom is discussed. © 2009 Wiley Periodicals, Inc. 相似文献
132.
David B. Rivers Michele Genco Rigoberto A. Sanchez 《In vitro cellular & developmental biology. Animal》1999,35(2):102-110
Summary The lethal effects of crude venom prepared from the ectoparasitic wasp Nasonia vitripennis were examined with cultured cells from six insect and two vertebrate species. Venom caused cells from Sarcophaga peregrina (NIH SaPe4), Drosophila melanogaster (CRL 1963), Trichoplusia ni (TN-368 and BTI-TN-5B1-4), Spodoptera frugiperda (SF-21AE), and Lymantria dispar (IPL-Ldfbc1) to round up, swell, and eventually die. Despite similar sensitivities and overlapping LC50 values [0.0004–0.0015 venom reservoir equivalents (VRE)/μl], profound differences were noted at the onset of cytotoxicity
among the six insect cell lines: over 80% of the NIH SaPe4 and SF21AE cells were nonviable within 1 h after addition of an
LC99 dose of venom, whereas the other cells required a 5–10-fold longer incubation period to produce mortality approaching 100%.
In contrast, cells from the grass frog, Rana pipiens (ICR-2A), and goldfish, Carassius auratus (CAR), showed little sensitivity to the venom: six venom reservoir equivalents were needed to induce 50% mortality in ICR-2A
cells [50% lethal concentration (LC50)=0.067 VRE/μl), and 9 VRE did not yield sufficient mortality in CAR cells for us to calculate an LC50. All susceptible cells showed similar responses when incubated with wasp venom: retraction of cytoplasmic extensions (when
present), blebbing of the plasma membrane, swelling of the plasma and nuclear membranes, condensation of nuclear material,
and eventual cell death attributed to lysis. The rate of swelling and lysis in NIH SaPe4 and BTI-TN-5B1-4 cells exposed to
venom appeared to be dependent on the diffusion potential of extracellular solutes (Na+=choline>sucrose≥raffinose>K+), which is consistent with a colloid-osmotic lysis mechanism of cell death. When T. ni cells were cotreated with venom and the K+ channel blocker 4-aminopyridine, cell swelling and lysis increased with increasing drug concentration. In contrast, cells
from S. peregrina were protected from the effects of the venom when treated in a similar manner. Addition of certain divalent cations (Zn+2 and Ca+2) to the extracellular media 1 h postvenom incubation rescued both BTI-TN-5B1-4 and NIH SaPe4 cells, suggesting that protection
was gained from closure of open pores rather than prevention of pore formation. Venom from N. vitripennis displayed no hemolytic activity toward sheep erythrocytes, supporting the view that venom intoxication is not by a nondiscriminate
mechanism. A possible mode of action of the venom is discussed. 相似文献
133.
W. C. Rivers 《BMJ (Clinical research ed.)》1905,1(2306):569-570
134.
Using cultured cells from bovine and rat aortas, we have examined the possibility that endothelial cells might regulate the growth of vascular smooth muscle cells. Conditioned medium from confluent bovine aortic endothelial cells inhibited the proliferation of growth-arrested smooth muscle cells. Conditioned medium from exponential endothelial cells, and from exponential or confluent smooth muscle cells and fibroblasts, did not inhibit smooth muscle cell growth. Conditioned medium from confluent endothelial cells did not inhibit the growth of endothelial cells or fibroblasts. In addition to the apparent specificity of both the producer and target cell, the inhibitory activity was heat stable and not affected by proteases. It was sensitive flavobacterium heparinase but not to hyaluronidase or chondroitin sulfate ABC lyase. It thus appears to be a heparinlike substance. Two other lines of evidence support this conclusion. First, a crude isolate of glycosaminoglycans (TCA-soluble, ethanol-precipitable material) from endothelial cell-conditioned medium reconstituted in 20 percent serum inhibited smooth muscle cell growth; glycosaminoglycans isolated from unconditioned medium (i.e., 0.4 percent serum) had no effect on smooth muscle cell growth. No inhibition was seen if the glycosaminoglycan preparation was treated with heparinase. Second, exogenous heparin, heparin sulfate, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate ABC, and hyaluronic acid were added to 20 percent serum and tested for their ability to inhibit smooth muscle cell growth. Heparin inhibited growth at concentrations as low as 10 ng/ml. Other glycosaminoglycans had no effect at doses up to 10 μg/ml. Anticoagulant and non- anticoagulant heparin were equally effective at inhibiting smooth muscle cell growth, as they were in vivo following endothelial injury (Clowes and Karnovsk. Nature (Lond.). 265:625-626, 1977; Guyton et al. Circ. Res. 46:625-634, 1980), and in vitro following exposure of smooth muscle cells to platelet extract (Hoover et al. Circ. Res. 47:578-583, 1980). We suggest that vascular endothelial cells may secrete a heparinlike substance in vivo which may regulate the growth of underlying smooth muscle cells. 相似文献
135.
Caunt CJ Armstrong SP Rivers CA Norman MR McArdle CA 《The Journal of biological chemistry》2008,283(39):26612-26623
Although many stimuli activate extracellular signal-regulated kinases 1 and 2 (ERK1/2), the kinetics and compartmentalization of ERK1/2 signals are stimulus-dependent and dictate physiological consequences. ERKs can be inactivated by dual specificity phosphatases (DUSPs), notably the MAPK phosphatases (MKPs) and atypical DUSPs, that can both dephosphorylate and scaffold ERK1/2. Using a cell imaging model (based on knockdown of endogenous ERKs and add-back of wild-type or mutated ERK2-GFP reporters), we explored possible effects of DUSPs on responses to transient or sustained ERK2 activators (epidermal growth factor and phorbol 12,13-dibutyrate, respectively). For both stimuli, a D319N mutation (which impairs DUSP binding) increased ERK2 activity and reduced nuclear accumulation. These stimuli also increased mRNA levels for eight DUSPs. In a short inhibitory RNA screen, 12 of 16 DUSPs influenced ERK2 responses. These effects were evident among nuclear inducible MKP, cytoplasmic ERK MKP, JNK/p38 MKP, and atypical DUSP subtypes and, with the exception of the nuclear inducible MKPs, were paralleled by corresponding changes in Egr-1 luciferase activation. Simultaneous removal of all JNK/p38 MKPs or nuclear inducible MKPs revealed them as positive and negative regulators of ERK2 signaling, respectively. The effects of JNK/p38 MKP short inhibitory RNAs were not dependent on protein neosynthesis but were reversed in the presence of JNK and p38 kinase inhibitors, indicating DUSP-mediated cross-talk between MAPK pathways. Overall, our data reveal that a large number of DUSPs influence ERK2 signaling. Together with the known tissue-specific expression of DUSPs and the importance of ERK1/2 in cell regulation, our data support the potential value of DUSPs as targets for drug therapy. 相似文献
136.
Intercalation of proflavine and a platinum derivative of proflavine into double-helical Poly(A) 下载免费PDF全文
The equilibria and kinetics of the interactions of proflavine (PR) and its platinum-containing derivative [PtCl(tmen)(2)HNC(13)H(7)(NHCH(2)CH(2))(2)](+) (PRPt) with double-stranded poly(A) have been investigated by spectrophotometry and Joule temperature-jump relaxation at ionic strength 0.1 M, 25 degrees C, and pH 5.2. Spectrophotometric measurements indicate that base-dye interactions are prevailing. T-jump experiments with polarized light showed that effects due to field-induced alignment could be neglected. Both of the investigated systems display two relaxation effects. The kinetic features of the reaction are discussed in terms of a two-step series mechanism in which a precursor complex DS(I) is formed in the fast step, which is then converted to a final complex in the slow step. The rate constants of the fast step are k(1) = (2.5 +/- 0.4) x 10(6) M(-1) s(-1), k(-1) = (2.4 +/- 0.1) x 10(3) s(-1) for poly(A)-PR and k(1) = (2.3 +/- 0.1) x 10(6) M(-1) s(-1), k(-1) = (1.6 +/- 0.2) x 10(3) s(-1) for poly(A)-PRPt. The rate constants for the slow step are k(2) = (4.5 +/- 0.5) x 10(2) s(-1), k(-2) = (1.7 +/- 0.1) x 10(2) s(-1) for poly(A)-PR and k(2) = 9.7 +/- 1.2 s(-1), k(-2) = 10.6 +/- 0.2 s(-1) for poly(A)-PRPt. Spectrophotometric measurements yield for the equilibrium constants and site size the values K = (4.5 +/- 0.1) x 10(3) M(-1), n = 1.3 +/- 0.5 for poly(A)-PR and K = (2.9 +/- 0.1) x 10(3) M(-1), n = 2.3 +/- 0.6 for poly(A)-PRPt. The values of k(1) are similar and lower than expected for diffusion-limited reactions. The values of k(-1) are similar as well. It is suggested that the formation of DS(I) involves only the proflavine residues in both systems. In contrast, the values of k(2) and k(-2) in poly(A)-PRPt are much lower than in poly(A)-PR. The results suggest that in the complex DS(II) of poly(A)-PRPt both proflavine and platinum residues are intercalated. In addition, a very slow process was detected and ascribed to the covalent binding of Pt(II) to the adenine. 相似文献
137.
138.
H?Bukulmez AL?Matthews CM?Sullivan C?Chen MJ?Kraay RC?Elston RW?Moskowitz VM?Goldberg ML?WarmanEmail author 《Arthritis research & therapy》2005,8(1):R25
In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA),
we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family
histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses
to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis
of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing
total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We
compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings
of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the
siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age
and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to
identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with
hip OA than in those with knee OA. 相似文献
139.
The action of venom from the ectoparasitic wasp, Nasonia vitripennis, was monitored by examining alterations in patterned muscular movements characteristic of pupariation and eclosion behavior in the flesh fly, Sarcophaga bullata. Venom injected into larvae prior to pupariation caused a dose-dependent delay in pupariation. Eventually, such larvae did pupariate, but puparia were abnormally formed. Barographic records revealed that all elements of pupariation behavior were present in venom-injected larvae, but pupariation behavior was not well synchronized with tanning, thus implying that the venom caused disruption in the temporal organization of central motor programs. When larvae were ligated and injected with venom posterior to the ligature, no response was evident in the posterior region, suggesting that the venom does not directly stimulate muscles or neuromuscular junctions. Injection of exogenous ecdysteroid into venom-injected larvae restored some elements of pupariation behavior, consistent with ecdysone's role in stimulating the release of anterior retraction factor and puparium tanning factor, two factors that are released from the CNS to regulate pupariation. When the venom was injected into newly emerged imagoes, the duration of extrication behavior was shortened, whereas all phases of post-eclosion behavior were lengthened. These observations imply that the venom affects CNS centers that regulate the muscular systems engaged in extrication and post-eclosion behavior. 相似文献
140.
Low-frequency calls produced by blue whales, Balaenoptera musculus , were recorded in the northeastern Pacific Ocean off central California. Two blue whales were sighted during a vessel-based marine mammal survey, and when sonobuoys were subsequently deployed, blue whale calls were recorded. A third recording was obtained during the survey from a blue whale that was not seen. Recordings with 15, 25, and 55 min of calls were obtained from these individuals. The three recordings all contain two-part, low-frequency calls with slight interindividual variation. The calls consist of an amplitude modulated (AM) signal with a mean center frequency of 16.5 Hz, followed by a downsweep whose mean center frequency sweeps from 18.2 Hz to 16.6 Hz. The recordings are compared with blue whale recordings from the Pacific and Atlantic Oceans. The geographic variability suggests that blue whale calls may be used as an acoustic indicator of stock identity. 相似文献