Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes

Greisberg, Justin; Wolf, Jennifer Moriatis; Wyman, James J.; Zou, Lijun; Terek, Richard M.

doi:10.1016/s0736-0266(01)00025-0

Cited by 41 publications

(31 citation statements)

References 20 publications

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“…Nifedipine (Nf), an L-type voltage sensitive Ca 2+ channel blocker, has been shown to inhibit dynamic mechanical strain induced upregulation of parathyroid hormone-related protein expression (Tanaka et al 2005), as well as prostaglandin E2 upregulation of insulin-like growth factor binding protein-3 expression and synthesis in chondrocytes (DiBattista et al 1996). Gadolinium (Gd), an inhibitor of cation-selective stretch-activated ion-channels, has been shown to increase proteoglycan synthesis at 4 mM and inhibit proliferation in a dose-dependent manner (Greisberg et al 2001). Thapsigargin (Tg), a natural plant product which depletes the Ca 2+ store in the sarcoplasmic and endoplasmic reticula by inhibiting ATPdependent Ca 2+ pumps, has been shown to inhibit protein production and secretion, as well as proteoglycan synthesis (but not GAG synthesis) (Clark et al 1994).…”

Section: Ion-channel Inhibitorsmentioning

confidence: 99%

Ion-channel Regulation of Chondrocyte Matrix Synthesis in 3D Culture Under Static and Dynamic Compression

Mouw

Imler

Levenston

2006

Biomech Model Mechanobiol

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Inhibition of various ion channels alters chondrocyte mechanotransduction in monolayer, but the mechanisms involved in chondrocyte mechanotransduction in three- dimensional culture remain unclear. The objective of this study was to investigate the effects of inhibiting putative ion-channel influenced mechanotransduction mechanisms on the chondrocyte responses to static and dynamic compression in three-dimensional culture. Bovine articular cartilage explants were used to investigate the dose-dependent inhibition and recovery of protein and sulfated glycosaminoglycan (sGAG) syntheses by four ion-channel inhibitors: 4-Aminopyridine (4AP), a K(+) channel blocker; Nifedipine (Nf), a Ca(2+) channel blocker; Gadolinium (Gd), a stretch-activated channel blocker; and Thapsigargin (Tg), which releases intracellular Ca(2+) stores by inhibiting ATP-dependent Ca(2+) pumps. Chondrocyte-seeded agarose gels were used to examine the influence of 20 h of static and dynamic loading in the presence of each of the inhibitors. Overall, treatment with the ion-channel inhibitors had a greater effect on sGAG synthesis, with the exception of Nf, which more substantially affected protein synthesis. Treatment with Tg significantly impaired both overall protein and sGAG synthesis, with a drastic reduction in sGAG synthesis. The inhibitors differentially influenced the responses to mechanical stimuli. Dynamic compression significantly upregulated protein synthesis but did not significantly affect sGAG synthesis with Nf or Tg treatment. Dynamic compression significantly upregulated both protein and sGAG synthesis rates with Gd treatment. There was no significant stimulation of either protein or sGAG synthesis by dynamic compression with 4AP treatment. Interruption of many ion-channel signaling mechanisms affected sGAG synthesis, suggesting a complicated, multi-pathway signaling process. Also, Ca(2+) signaling may be critical for the transduction of mechanical stimulus in regulating sGAG synthesis. This modulation potentially occurs through direct interactions with the extracellular matrix.

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Section: Ion-channel Inhibitorsmentioning

confidence: 99%

Ion-channel Regulation of Chondrocyte Matrix Synthesis in 3D Culture Under Static and Dynamic Compression

Mouw

Imler

Levenston

2006

Biomech Model Mechanobiol

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“…The dual effects of lanthanides were discussed on the basis of bi-directional dose dependence (Wang et al 1999). The proapoptosis effect frequently appeared at the concentration higher up to millimolar levels (Mizgerd et al 1996;Sato et al 1998;Greisberg et al 2001;Dai et al 2002;Shi and Huang 2005), while proliferative effect often occured at micromolar concentration (Yu et al 2005(Yu et al , 2006Fu et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Gadolinium promoted proliferation and enhanced survival in human cervical carcinoma cells

Zhang

et al. 2009

Biometals

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The effect of gadolinium chloride (Gd) on the proliferation of HeLa cells was investigated at lower concentration. The results obtained by MTT and cell cycle analysis showed that Gd promoted proliferation by inducing S phase entry in HeLa cells at the concentration less than 100 microM. It was further evidenced by both an increase in the levels of phosphorylation of retinoblastoma protein (pRb) and a remarkable increase in cyclin E expression. Moreover, the survival of cells, exposed to Gd up to 3-5 days, was increased compared with control. The attenuation of the serum deprivation-induced cell loss by Gd was associated with the sustained activation of FAK (PY(397)) and the delayed activation of JNKs pathway. Besides, it appeared that Gd promoted cell proliferation and survival in HeLa cells was not contributed to the ROS generation. Based on the present results, both positive and negative effects of the lanthanides as potential drugs or diagnostic agents are discussed.

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“…The effect of gadolinium in inducing the apoptosis macrophage was investigated by Mizgerd et al (1996), according to this 10 minutes making cells subject to gadolinium, significantly induces cell death through the induction of the apoptosis mechanism up to 24 hours (Mizgerd et al, 1996). Further, Greisberg et al (2001) described that gadodiamide increases the production of proteoglycans, decreases the cell birth and induces apoptosis in chondrocyte. Greisberg et al (2001) investigated the effect of short term placement of chondrocyte to gadolinium.…”

Section: Discussionmentioning

confidence: 99%

“…Further, Greisberg et al (2001) described that gadodiamide increases the production of proteoglycans, decreases the cell birth and induces apoptosis in chondrocyte. Greisberg et al (2001) investigated the effect of short term placement of chondrocyte to gadolinium. The cell growth was reduced while exposing to gadolinium (in a dose-dependent manner) and chondrocyte apoptosis was also induced in a dose-dependent manner (Greisberg et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Greisberg et al (2001) investigated the effect of short term placement of chondrocyte to gadolinium. The cell growth was reduced while exposing to gadolinium (in a dose-dependent manner) and chondrocyte apoptosis was also induced in a dose-dependent manner (Greisberg et al, 2001). Salakou et al (2007) conducted study on patients with myasthenia gravis underwent cystectomy, Bcl2 ratio to Bax was measured in patients with different disease classifications.…”

Section: Discussionmentioning

confidence: 99%

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Effect of magnevist conjugated dendrimer on Bax/Bcl2 gene expression levels in MCF-7 cancer cells

Fattah¹,

Javani²,

Saffari³

et al. 2016

JEBAS

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KEYWORDS Magnevist conjugated dendrimerReal-time PCR MCF-7 ApoptosisCorona protein ABSTRACTIn recent years, investigating pharmacogenetics and effects of corona protein nanomaterial in biological applications has been seriously considered for the treatment of human diseases. In this study, the mechanism of apoptosis induced by Magnevist conjugated dendrimer was investigated to compare Magnevist as a contrasting agent on MCF-7 cells. Cytotoxicity effects of new Magnevist conjugated dendrimer was evaluated by using MTT assay. Also, In order to demonstrate the effect of drugs on the apoptosis, a quantitative method real-time PCR was used. The interaction of plasma proteins was investigated by Magnevist conjugated dendrimer compared with Magnevist using SDS-PAGE technique to determine the fate of nanoparticles. Result of study revealed that it quite significantly affects Bax and increasing apoptosis. Its effect on Bcl2 is more than net gadopentetic acid and almost equivalent to the effect of dendrimer alone. In fact, a significant increase was observed in Bax compared to the control group, and no significant effect was observed on BCL2 gene. Also, corona protein was investigated and the protein with weight less than 70 kDa was observed around a nanoparticle that seems albumin protein with a molecular weight of 67 kDa. Conducted study revealed the acceptable therapeutic effect of Magnevist conjugated dendrimer and it was comparable with in vitro Magnevist model of breast cancer. Therefore, the use of the denderimer can be effective on increasing expression of some proapoptoticgenes and provided a new perspective in clinical diagnostic.

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Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes

Cited by 41 publications

References 20 publications

Ion-channel Regulation of Chondrocyte Matrix Synthesis in 3D Culture Under Static and Dynamic Compression

Ion-channel Regulation of Chondrocyte Matrix Synthesis in 3D Culture Under Static and Dynamic Compression

Gadolinium promoted proliferation and enhanced survival in human cervical carcinoma cells

Effect of magnevist conjugated dendrimer on Bax/Bcl2 gene expression levels in MCF-7 cancer cells

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