Cadmium‐induced Cytosolic Ca<sup>2+</sup> Elevation and Subsequent Apoptosis in Renal Tubular Cells

Yeh, Jeng-Hsien; Huang, Chorng-Chih; Yeh, Malcolm; Wang, Jyh-Seng; Lee, Jenn-Kuen; Jan, Chung‐Ren

doi:10.1111/j.1742-7843.2009.00391.x

Cited by 30 publications

(32 citation statements)

References 39 publications

(46 reference statements)

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“…This is followed by ROS generation in a second, slower phase together with Fe mobilization leading to mitochondrial membrane lipid peroxidation. In accordance with most animal-based studies, Cd-induced cellular processes in plants also include mitochondrial ROS production (Yeh et al 2009). …”

Section: Mitochondrial Ros Productionmentioning

confidence: 75%

“…Several studies focus on apoptosis as an important process mediating Cd-toxicity in different organs (Hamada et al 1997;Shih et al 2004;Oh and Lim 2006;Coonse et al 2007;Lasfer et al 2008;Hossain et al 2009;Wang et al 2009;Yeh et al 2009;Zhou et al 2009), but non-apoptotic cell death is also apparent (Kim et al 2010;Belyaeva et al 2006Belyaeva et al , 2008Sancho et al 2006). When applied in low to moderate concentrations under in vivo and in vitro conditions, Cd mainly causes apoptosis (Sancho et al 2006).…”

Section: Cadmium: An Oxidative Challengementioning

confidence: 95%

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Cadmium stress: an oxidative challenge

et al. 2010

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At the cellular level, cadmium (Cd) induces both damaging and repair processes in which the cellular redox status plays a crucial role. Being not redox-active, Cd is unable to generate reactive oxygen species (ROS) directly, but Cd-induced oxidative stress is a common phenomenon observed in multiple studies. The current review gives an overview on Cd-induced ROS production and anti-oxidative defense in organisms under different Cd regimes. Moreover, the Cd-induced oxidative challenge is discussed with a focus on damage and signaling as downstream responses. Gathering these data, it was clear that oxidative stress related responses are affected during Cd stress, but the apparent discrepancies observed in between the different studies points towards the necessity to increase our knowledge on the spatial and temporal ROS signature under Cd stress. This information is essential in order to reveal the exact role of Cd-induced oxidative stress in the modulation of downstream responses under a diverse array of conditions.

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Section: Mitochondrial Ros Productionmentioning

confidence: 75%

Section: Cadmium: An Oxidative Challengementioning

confidence: 95%

Cadmium stress: an oxidative challenge

et al. 2010

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“…However, other triggers may also be involved in the induction of ER stress by cadmium. Several recent reports suggest release of calcium from the ER mediates cadmium-induced apoptosis in renal tubular cells and other cell types (Xie et al 2010;Yeh et al 2009). Depletion of calcium store in the ER is a well-known trigger to induce ER stress.…”

Section: Future Perspectivesmentioning

confidence: 97%

The oxidative stress: endoplasmic reticulum stress axis in cadmium toxicity

2010

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Cadmium preferentially accumulates in the kidney, the major target for cadmium-related toxicity. Several underlying mechanisms are postulated, and reactive oxygen species (ROS) have been considered as crucial mediators for tissue injuries. In addition to oxidative stress, we recently disclosed that endoplasmic reticulum (ER) stress also plays a critical role. Cadmium causes ER stress in vitro and in vivo and mediates induction of apoptosis in target tissues. In this article, we describe a role for ER stress and involvement of particular branches of the unfolded protein response (UPR) in cadmium-triggered tissue injury, especially nephrotoxicity. We also discuss relationship between oxidative stress and ER stress, and involvement of selective ROS in the induction of pro-apoptotic branches of the UPR.

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“…Studies have shown that Cd disrupts intracellular free calcium ([Ca 2+ ] i ) homeostasis, leading to apoptosis in a variety of cells, such as skin epidermal cells [15], hepatic cells [16], [17], lymphoblastoid cells [16], mesangial cells [18]–[20], renal tubular cells [21], [22], astrocytes [23], NIH 3T3 cells [24], thyroid cancer cells [25], and thymocytes [26]. As a second messenger, Ca 2+ mediates physiological responses of neurons to neurotransmitters and neurotrophic factors [27]–[29].…”

Section: Introductionmentioning

confidence: 99%

Calcium Signaling Is Involved in Cadmium-Induced Neuronal Apoptosis via Induction of Reactive Oxygen Species and Activation of MAPK/mTOR Network

et al. 2011

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Cadmium (Cd), a toxic environmental contaminant, induces oxidative stress, leading to neurodegenerative disorders. Recently we have demonstrated that Cd induces neuronal apoptosis in part by activation of the mitogen-activated protein kineses (MAPK) and mammalian target of rapamycin (mTOR) pathways. However, the underlying mechanism remains elusive. Here we show that Cd elevated intracellular calcium ion ([Ca2+]i) level in PC12, SH-SY5Y cells and primary murine neurons. BAPTA/AM, an intracellular Ca2+ chelator, abolished Cd-induced [Ca2+]i elevation, and blocked Cd activation of MAKPs including extracellular signal-regulated kinase 1/2 (Erk1/2), c-Jun N-terminal kinase (JNK) and p38, and mTOR-mediated signaling pathways, as well as cell death. Pretreatment with the extracellular Ca2+ chelator EGTA also prevented Cd-induced [Ca2+]i elevation, MAPK/mTOR activation, as well as cell death, suggesting that Cd-induced extracellular Ca2+ influx plays a critical role in contributing to neuronal apoptosis. In addition, calmodulin (CaM) antagonist trifluoperazine (TFP) or silencing CaM attenuated the effects of Cd on MAPK/mTOR activation and cell death. Furthermore, Cd-induced [Ca2+]i elevation or CaM activation resulted in induction of reactive oxygen species (ROS). Pretreatment with BAPTA/AM, EGTA or TFP attenuated Cd-induced ROS and cleavage of caspase-3 in the neuronal cells. Our findings indicate that Cd elevates [Ca2+]i, which induces ROS and activates MAPK and mTOR pathways, leading to neuronal apoptosis. The results suggest that regulation of Cd-disrupted [Ca2+]i homeostasis may be a new strategy for prevention of Cd-induced neurodegenerative diseases.

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Cadmium‐induced Cytosolic Ca²⁺ Elevation and Subsequent Apoptosis in Renal Tubular Cells

Cited by 30 publications

References 39 publications

Cadmium stress: an oxidative challenge

Cadmium stress: an oxidative challenge

The oxidative stress: endoplasmic reticulum stress axis in cadmium toxicity

Calcium Signaling Is Involved in Cadmium-Induced Neuronal Apoptosis via Induction of Reactive Oxygen Species and Activation of MAPK/mTOR Network

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Cadmium‐induced Cytosolic Ca2+ Elevation and Subsequent Apoptosis in Renal Tubular Cells

Cited by 30 publications

References 39 publications

Cadmium stress: an oxidative challenge

Cadmium stress: an oxidative challenge

The oxidative stress: endoplasmic reticulum stress axis in cadmium toxicity

Calcium Signaling Is Involved in Cadmium-Induced Neuronal Apoptosis via Induction of Reactive Oxygen Species and Activation of MAPK/mTOR Network

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Cadmium‐induced Cytosolic Ca²⁺ Elevation and Subsequent Apoptosis in Renal Tubular Cells