Duality of effect of La3+ on mitochondrial permeability transition pore depending on the concentration

Dong, Shuai; Zhao, Yuebin; Liu, Huixue; Yang, Xiaoda; Wang, Kui

doi:10.1007/s10534-009-9244-1

Cited by 16 publications

(21 citation statements)

References 29 publications

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“…Besides the ER, the Golgi apparatus (Chandra et al 1991;Zha et al 1995) and mitochondria (Gunter et al 1994;Werth and Thayer 1994) are other important sources of intracellular Ca 2+ . La 3+ can reportedly displace mitochondrial Ca 2+ (Dong et al 2009). As shown in Fig.…”

Section: Discussionmentioning

confidence: 96%

Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca2+

et al. 2010

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Gadolinium (Gd) and its complexes are utilized widely in industrial and clinical diagnoses. As a rare earth metal ion, free gadolinium (Gd(3+)) in the human body poses neurotoxic risks during its in vivo release and retention. In the central nervous system, astrocytes play a pivotal role in processing toxic metal ions. The present study evaluates the effects of Gd on cellular calcium homeostasis, a common mechanism that causes cell death, and on unfolded protein responses (UPRs), a mechanism for cell survival in response to toxic stimuli in mammalian cells. The experimental results indicate that the influx of extracellular Ca(2+) increases greatly after the exposure of astrocytes to Gd; however, no cell deaths were observed. Further evidence suggests the up-regulated expression of the endoplasmic reticulum (ER)-resident chaperone protein GRP78 by ER stress-mediated signal transductions, specifically the activation of ATF6, eIF2a, and IRE1. These results suggest that Gd promotes Ca(2+) influx, thus triggering UPRs, which can be closely associated to the resistance of astrocytes to Gd-induced cytotoxicity.

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Section: Discussionmentioning

confidence: 96%

Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca2+

et al. 2010

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“…Interestingly, mitochondria are both the source and target of ROS (Simon et al 2000). The previous report Dong et al 2009) and our previous studies (Shen et al 2009b, c) on [LaCit 2 ] 3-and [YbCit 2 ] 3--induced HeLa cells apoptosis have shown that cell apoptosis promoted by rare earth complexes may be related to mitochondrial apoptosis pathway and that ROS were involved in the mechanism. Similar to the result of [LaCit 2 ] 3-and [YbCit 2 ] 3-on HeLa cells, these altered proteins in [LaCit 2 ] 3--treated SiHa cells can be classified into several categories, including the proteins involved in apoptosis and cell proliferation, stress response and redox activity, and translation and protein synthesis.…”

Section: Discussionmentioning

confidence: 82%

Proteomic analysis of lanthanum citrate-induced apoptosis in human cervical carcinoma SiHa cells

et al. 2010

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Lanthanides possess diverse biological effect and have been shown to promote cell proliferation and induce apoptosis. Our previous studies showing that lanthanide citrate complex has significant antitumor activity in human cervical cancer HeLa cells. This study aims at determining if [LaCit(2)](3-) have the activity against another type of human cervical cancer cell line SiHa and the changes in protein expression that contribute to the mechanism(s) of [LaCit(2)](3-)-mediated apoptosis in SiHa cells. Cell growth inhibition was measured by MTT method, and apoptosis was detected by means of Hoechst 33258 staining and flow cytometry analysis. After [LaCit(2)](3-)-treatment the results show that the growth of SiHa cells was inhibited, the cells displayed typical apoptosis morphological changes, and increase in the rates of apoptosis. Using proteomics approaches, a variety of differentially expressed proteins were identified in SiHa cells before and after treatment with [LaCit(2)](3-). There were profound changes in 10 proteins relating to mitochondrial function and oxidative stress, suggesting that mitochondrial dysfunction plays a key role in [LaCit(2)](3-)-induced apoptosis. This was confirmed by a decrease in the mitochondrial transmembrane potential (Δψ(m)), and increases in H(2)O(2) generation in [LaCit(2)](3-)-treated cells. Among them the alerted proteins, Prx I, ANXA1 and TRAF5 were validated by western blotting analyses. These results suggest that there is an intrinsic molecular pathway of cell apoptosis in [LaCit(2)](3-)-treated SiHa cells. This observation is in accordance with our previous reports about the effects of [LaCit(2)](3-) and [YbCit(2)](3-) on HeLa cells and it provide a molecular mechanism underlying lanthanide citrate complex-mediated cell apoptosis.

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“…Data are normalized to the density of -actin and are the mean ± SD of three independent experiments (*p < 0.05, **p < 0.01, compared with the control group). stimulation of ROS generation through interaction with mitochondria is involved in the mechanisms of cytotoxicity of lanthanide ions [17,18]. In this work, in order to explore the potential neurotoxicity of Gd 3+ , we investigated the effects of GdCl 3 on neurons both in the presence and the absence of astrocytes by use of a Transwell co-culture method as indicated in Figure 1.…”

Section: Discussionmentioning

confidence: 99%

“…Submicromolar concentrations of La 3+ have been shown to stimulate mitochondrial ROS generation by acting as a Ca 2+ analog [18] and Gd 3+ may increase ROS production in a similar way.…”

Section: Discussionmentioning

confidence: 99%

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Brain-derived neurotrophic factor protects neurons from GdCl3-induced impairment in neuron-astrocyte co-cultures

et al. 2010

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Gadolinium (Gd 3+ ) complexes are important contrast agents in medical magnetic resonance imaging (MRI) and of great potential value in brain research. In order to better understand the mechanisms of the action of Gd 3+ on neurons in the complex central nervous system (CNS), the neurotoxic actions of GdCl 3 have been investigated in both neuron monoculture and astrocyteneuron co-culture systems. Measurements of lactate dehydrogenase release showed that GdCl 3 causes significant cell death of monocultured neurons as a result of reactive oxygen species (ROS) generation and down-regulation of brain-derived neurotrophic factor (BDNF). However, GdCl 3 does not affect the viability and BDNF expression of astrocytes. Both co-culturing of neurons with astrocytes and addition of BDNF ameliorated GdCl 3 -induced neurotoxicity by decreasing ROS generation and facilitating recovery of BDNF levels. The results obtained suggest that astrocytes in the CNS may protect neurons from GdCl 3 -induced impairment through secreting BDNF and thus up-regulating BDNF expression and interfering with Gd 3+ -induced cell signaling in neurons. A possible molecular mechanism is suggested which should be helpful in understanding the neurotoxic actions of gadolinium probes . gadolinium, brain-derived neurotrophic factor, BDNF, co-culture, astrocytes, neurons

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Duality of effect of La3+ on mitochondrial permeability transition pore depending on the concentration

Cited by 16 publications

References 29 publications

Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca2+

Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca2+

Proteomic analysis of lanthanum citrate-induced apoptosis in human cervical carcinoma SiHa cells

Brain-derived neurotrophic factor protects neurons from GdCl3-induced impairment in neuron-astrocyte co-cultures

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