Effect of melamine on [Ca2+]i and viability in PC3 human prostate cancer cells

Yu, Chia‐Cheng; Chou, Chiang-Ting; Sun, Te-Kung; Liang, Wei; Cheng, Jin‐Shiung; Chang, Hong‐Tai; Wang, Jue‐Long; Tseng, Hui‐Wen; Kuo, Chun-Chi; Chen, Fu‐An; Kuo, Daih‐Huang; Shieh, Pochuen; Jan, Chung‐Ren

doi:10.1016/j.etap.2014.09.013

Cited by 2 publications

(1 citation statement)

References 30 publications

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“…Moreover, comparison between doses of melamine-treated cells shows greater incidences of apoptosis then necrosis at lower doses, whereas necrosis starts during exposure to higher doses (23,52). Our explanation is that the first phase of melamine activation at low to moderate doses may deplete ER Ca 2ϩ stores and further stimulate Ca 2ϩ entry across the plasma membrane, thus producing a prolonged [Ca 2ϩ ] i rise in the cytosol attributable to sustained Ca 2ϩ entry, leading to ER stress and apoptosis (55). In contrast, moderate to high doses of melamine induce cytotoxicity, resulting in necrosis.…”

Section: Discussionmentioning

confidence: 77%

Melamine induces Ca²⁺-sensing receptor activation and elicits apoptosis in proximal tubular cells

Yiu

Ibeh

Roy

et al. 2017

American Journal of Physiology-Cell Physiology

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Melamine causes renal tubular cell injury through inflammation, fibrosis, and apoptosis. Although melamine affects the rise in intracellular Ca concentration ([Ca]) reactive oxygen species (ROS) production, and proapoptotic pathway activation, the mechanism of upstream Ca signaling is unknown. Because melamine has some structural similarities with l-amino acids, which endogenously activate Ca-sensing receptors (CSR), we examined the effect of melamine on CSR-induced Ca signaling and apoptotic cell death. We show here that melamine activates CSR, causing a sustained Ca entry in the renal epithelial cell line, LLC-PK1. Moreover, such CSR stimulation resulted in a rise in [Ca], leading to enhanced ROS production. Furthermore, melamine-induced elevated [Ca] and ROS production caused a dose-dependent increase in apoptotic (by DAPI staining, DNA laddering, and annexin V assay) and necrotic (propidium iodide staining) cell death. Upon examining the downstream mechanism, we found that transforming growth factor β1 (TGF-β1), which increases extracellular matrix genes and proapoptotic signaling, was also upregulated at lower doses of melamine, which could be due to an early event inducing apoptosis. Additionally, cells exposed to melamine displayed a rise in pERK activation and lactate dehydrogenase release resulting in cytotoxicity. These results offer a novel insight into the molecular mechanisms by which melamine exerts its effect on CSR, causing a sustained elevation of [Ca], leading to ROS generation, fibronectin production, proapoptotic pathway activation, and renal cell damage. Together, these results thus suggest that melamine-induced apoptosis and/or necrosis may subsequently result in acute kidney injury and promote kidney stone formation.

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Section: Discussionmentioning

confidence: 77%

Melamine induces Ca²⁺-sensing receptor activation and elicits apoptosis in proximal tubular cells

Yiu

Ibeh

Roy

et al. 2017

American Journal of Physiology-Cell Physiology

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Melamine, beyond the kidney: A ubiquitous endocrine disruptor and neurotoxicant?

2017

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Effect of melamine on [Ca2+]i and viability in PC3 human prostate cancer cells

Cited by 2 publications

References 30 publications

Melamine induces Ca²⁺-sensing receptor activation and elicits apoptosis in proximal tubular cells

Melamine induces Ca²⁺-sensing receptor activation and elicits apoptosis in proximal tubular cells

Melamine, beyond the kidney: A ubiquitous endocrine disruptor and neurotoxicant?

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Effect of melamine on [Ca2+]i and viability in PC3 human prostate cancer cells

Cited by 2 publications

References 30 publications

Melamine induces Ca2+-sensing receptor activation and elicits apoptosis in proximal tubular cells

Melamine induces Ca2+-sensing receptor activation and elicits apoptosis in proximal tubular cells

Melamine, beyond the kidney: A ubiquitous endocrine disruptor and neurotoxicant?

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Melamine induces Ca²⁺-sensing receptor activation and elicits apoptosis in proximal tubular cells

Melamine induces Ca²⁺-sensing receptor activation and elicits apoptosis in proximal tubular cells