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Related Concept Videos

MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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Crosstalk Between miRNA and Protein Expression Profiles in Nitrate-Exposed Brain Cells.

Saumya Mishra1,2, Sana Sarkar1, Anuj Pandey1

  • 1Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226001, India.

Molecular Neurobiology
|March 27, 2023
PubMed
Summary

High nitrate levels significantly alter brain cell function by deregulating microRNAs and proteins, impacting mitochondrial health. Lower nitrate doses showed no adverse effects, suggesting a dose-dependent toxicity.

Keywords:
Cellular bioenergeticsHMC3 cellsNitrateProteomicsSH-SY5Y cellsmiRNAs

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Area of Science:

  • Neuroscience
  • Toxicology
  • Molecular Biology

Background:

  • Nitrate ingestion is linked to adverse human health outcomes, particularly neurodevelopmental issues.
  • Environmental nitrate levels are increasing, raising concerns about potential future health impacts.

Purpose of the Study:

  • To investigate the molecular effects of environmentally relevant and high nitrate doses on human neuroblastoma (SH-SY5Y) and microglial (HMC3) cells.
  • To identify deregulated microRNAs (miRNAs) and proteins in response to nitrate exposure.

Main Methods:

  • Cells were exposed to two nitrate doses (X: 320 mg/L and 5X: 1600 mg/L) for 72 hours.
  • High-throughput OpenArray and LC-MS analyses were used to profile miRNA and protein expression.
  • Mitochondrial bioenergetics, including oxygen consumption rate (OCR), were measured.

Main Results:

  • The 5X nitrate dose caused significant deregulation of miRNAs (e.g., miR-34b, miR-34c, miR-155) and proteins in both cell types.
  • Deregulated miRNAs targeted proteins involved in crucial cellular processes like metabolism, mitochondrial function, apoptosis, and brain development.
  • A 5X nitrate dose markedly reduced mitochondrial oxygen consumption rate and other bioenergetic parameters.
  • The X dose of nitrate did not induce any significant adverse effects.

Conclusions:

  • High nitrate exposure (5X dose) significantly disrupts cellular physiology and function in neuronal and microglial cells by altering miRNA and protein expression.
  • These molecular changes impact key pathways essential for brain health, including mitochondrial function and homeostasis.
  • The findings highlight the potential neurotoxic risks associated with high nitrate levels, while lower, environmentally prevalent doses appear safe.