Cadmium Disrupted ER Ca2+ Homeostasis by Inhibiting SERCA2 Expression and Activity to Induce Apoptosis in Renal Proximal Tubular Cells

Li, Kongdong; Guo, Chuanzhi; Ruan, Jiacheng; Niu, Bo; Wong, Chris K C; Shi, Haifeng; Gu, Jie

doi:10.3390/ijms24065979

Cited by 8 publications

(4 citation statements)

References 42 publications

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“…The disruption of calcium homeostasis has been suggested to be another mechanism by which Cd induces tubular cell death [131][132][133]. In primary rat proximal tubular cells, Cd caused calcium release from the endoplasmic reticulum, which raised intracellular calcium concentrations and inhibited autophagy [131,132].…”

Section: Mitochondrial Dysfunction and Calcium Homeostasis Disruptionmentioning

confidence: 99%

“…In mouse renal tubular cells, Cd appeared to activate at least two calcium channels, namely phospholipase C (PLC)-inositol 1, 4, 5-trisphosphate receptor (IP3R) and the sarco/endoplasmic reticulum Ca2 + -ATPase (SERCA), known to be involved in the release and reuptake of calcium by the ER [132]. Cd also suppressed SERCA expression and diminished the stability of the SERCA protein in mouse tubular epithelial cells, thereby intensifying the toxic effects of Cd [133].…”

Section: Mitochondrial Dysfunction and Calcium Homeostasis Disruptionmentioning

confidence: 99%

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Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

Satarug

2024

Biomedicines

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Cadmium (Cd) is a metal with no nutritional value or physiological role. However, it is found in the body of most people because it is a contaminant of nearly all food types and is readily absorbed. The body burden of Cd is determined principally by its intestinal absorption rate as there is no mechanism for its elimination. Most acquired Cd accumulates within the kidney tubular cells, where its levels increase through to the age of 50 years but decline thereafter due to its release into the urine as the injured tubular cells die. This is associated with progressive kidney disease, which is signified by a sustained decline in the estimated glomerular filtration rate (eGFR) and albuminuria. Generally, reductions in eGFR after Cd exposure are irreversible, and are likely to decline further towards kidney failure if exposure persists. There is no evidence that the elimination of current environmental exposure can reverse these effects and no theoretical reason to believe that such a reversal is possible. This review aims to provide an update on urinary and blood Cd levels that were found to be associated with GFR loss and albuminuria in the general populations. A special emphasis is placed on the mechanisms underlying albumin excretion in Cd-exposed persons, and for an accurate measure of the doses–response relationships between Cd exposure and eGFR, its excretion rate must be normalised to creatinine clearance. The difficult challenge of establishing realistic Cd exposure guidelines such that human health is protected, is discussed.

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Section: Mitochondrial Dysfunction and Calcium Homeostasis Disruptionmentioning

confidence: 99%

Section: Mitochondrial Dysfunction and Calcium Homeostasis Disruptionmentioning

confidence: 99%

Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

Satarug

2024

Biomedicines

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“…Cadmium not only competes with calcium channels for entry but also stimulates them, leading to excessive accumulation of calcium in different cellular compartments [46]. As a result, it may induce apoptotic cell death [46,47].…”

Section: The Toxicity Of Cadmium Compoundsmentioning

confidence: 99%

“…Cd(II) is also able to affect signaling pathways in the cell. For instance, cadmium not only is a competitive substrate for calcium channels but also activates them, providing means for the hyperaccumulation of calcium in distinct cellular compartments and dysregulating calcium-dependent signaling pathways [46,47]. Cadmium is also able to hijack other divalent ion uptake pathways.…”

Section: Degradation Of Membrane Proteins In Response To Cadmium Stressmentioning

confidence: 99%

Multilevel Regulation of Membrane Proteins in Response to Metal and Metalloid Stress: A Lesson from Yeast

Zbieralski,

Staszewski,

Konczak

et al. 2024

IJMS

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In the face of flourishing industrialization and global trade, heavy metal and metalloid contamination of the environment is a growing concern throughout the world. The widespread presence of highly toxic compounds of arsenic, antimony, and cadmium in nature poses a particular threat to human health. Prolonged exposure to these toxins has been associated with severe human diseases, including cancer, diabetes, and neurodegenerative disorders. These toxins are known to induce analogous cellular stresses, such as DNA damage, disturbance of redox homeostasis, and proteotoxicity. To overcome these threats and improve or devise treatment methods, it is crucial to understand the mechanisms of cellular detoxification in metal and metalloid stress. Membrane proteins are key cellular components involved in the uptake, vacuolar/lysosomal sequestration, and efflux of these compounds; thus, deciphering the multilevel regulation of these proteins is of the utmost importance. In this review, we summarize data on the mechanisms of arsenic, antimony, and cadmium detoxification in the context of membrane proteome. We used yeast Saccharomyces cerevisiae as a eukaryotic model to elucidate the complex mechanisms of the production, regulation, and degradation of selected membrane transporters under metal(loid)-induced stress conditions. Additionally, we present data on orthologues membrane proteins involved in metal(loid)-associated diseases in humans.

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From ferroptosis to cuproptosis, and calcicoptosis, to find more novel metals-mediated distinct form of regulated cell death

Gu,

Guo,

Ruan

et al. 2024

Apoptosis

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Cadmium Disrupted ER Ca2+ Homeostasis by Inhibiting SERCA2 Expression and Activity to Induce Apoptosis in Renal Proximal Tubular Cells

Cited by 8 publications

References 42 publications

Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

Multilevel Regulation of Membrane Proteins in Response to Metal and Metalloid Stress: A Lesson from Yeast

From ferroptosis to cuproptosis, and calcicoptosis, to find more novel metals-mediated distinct form of regulated cell death

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