Cadmium hijacks the high zinc response by binding and activating the HIZR-1 nuclear receptor Original paper
Researched by:
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Metals
Metals
OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]
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Divine Aleru
Read More
Researched by:
-
Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study investigated how cadmium exposure affects the high zinc response in organisms by binding to and activating the HIZR-1 nuclear receptor, a key transcription factor involved in zinc homeostasis. The researchers focused on how cadmium, a toxic heavy metal, hijacks the high zinc response by functioning as a zinc mimetic. They explored cadmium’s ability to bind to the HIZR-1 ligand-binding domain and cause nuclear accumulation, leading to transcriptional activation through the high zinc activation (HZA) enhancer.
Who was studied?
The study utilized Caenorhabditis elegans (C. elegans), a model organism commonly used for understanding metal toxicity and cellular responses. Transgenic C. elegans animals expressing fusion proteins (HIZR-1::GFP) were exposed to various metal ions, including cadmium and zinc, to study the nuclear accumulation and transcriptional activation processes. Mutant strains with specific gene knockouts were also used to assess the role of HIZR-1 in cadmium response.
Most important findings
The study demonstrated that cadmium directly binds to the ligand-binding domain of HIZR-1, similarly to zinc, and induces its nuclear accumulation in intestinal cells. This process activates transcription via the HZA enhancer. Many genes activated by cadmium overlapped with those activated by high zinc, supporting the idea that cadmium hijacks the high zinc homeostasis system. Importantly, HIZR-1 was found to be essential for the transcriptional activation of certain genes in response to cadmium. However, not all cadmium-activated genes required HIZR-1, suggesting that multiple mechanisms regulate cadmium. Cadmium exposure led to the nuclear accumulation of HIZR-1 and activated the transcription of genes that are typically upregulated during zinc homeostasis.
Key implications
This research reveals an unexpected mechanism by which cadmium mimics zinc’s actions and activates the high zinc response. Cadmium, typically known for its toxic effects, functions as a ligand for HIZR-1, an essential receptor for regulating zinc homeostasis. Understanding how cadmium interacts with HIZR-1 could provide insight into cadmium’s toxicological mechanisms, potentially guiding new therapeutic strategies for cadmium exposure. The study also highlights how heavy metals can manipulate cellular pathways that normally maintain metal homeostasis, offering new avenues for investigating metal-induced toxicity and resistance mechanisms.
Cadmiun (Cd)
Cadmium (Cd) is a highly toxic heavy metal commonly found in industrial, agricultural, and environmental settings. Exposure to cadmium can occur through contaminated water, food, soil, and air, and it has been linked to a variety of health issues, including kidney damage, osteoporosis, and cancer. In agriculture, cadmium is often present in phosphate fertilizers and can accumulate in plants, entering the food chain. Its toxicity to living organisms makes cadmium a subject of regulatory concern worldwide, particularly in industrial waste disposal and environmental monitoring.
Zinc
Zinc is an essential trace element vital for cellular functions and microbiome health. It influences immune regulation, pathogen virulence, and disease progression in conditions like IBS and breast cancer. Pathogens exploit zinc for survival, while therapeutic zinc chelation can suppress virulence, rebalance the microbiome, and offer potential treatments for inflammatory and degenerative diseases.