Related Experiment Video

Updated: Jul 7, 2025

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
06:12

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

1.9K

YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths

Jiebo Lin1,2, Guankai Zhan1,2, Jinfeng Liu1,2,3

  • 1Women's Hospital, The Fourth Affiliated Hospital, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006.

National Science Review
|December 28, 2023
PubMed

Insights

Fluorene-9-bisphenol (BHPF) exposure downregulates the RNA regulator YTHDF2, causing tissue-specific cell death. This discovery reveals a new mechanism of programmed cell death (PCD) and highlights BHPF as a potential health risk.

Area of Science:

  • Epigenetics and RNA biology
  • Toxicology and environmental health
  • Developmental biology

Background:

  • N6-methyladenosine (m6A) is a key RNA regulator, but its tissue-specific functions are not fully understood.
  • Bisphenol A (BPA) substitutes like fluorene-9-bisphenol (BHPF) are common, and BHPF has been detected in pregnant individuals.
  • Tissue-specific programmed cell death (PCD) mechanisms require further elucidation.

Purpose of the Study:

  • To investigate the role of m6A reader YTHDF2 in tissue-specific PCD induced by BHPF.
  • To explore the molecular mechanisms underlying BHPF-mediated toxicity.
  • To assess the potential health risks of BHPF exposure.

Main Methods:

  • Investigated eight common BPA substitutes for BHPF detection in human serum samples.
  • Utilized a zebrafish model to study BHPF-induced tissue-specific PCD.
  • Analyzed the impact of BHPF on YTHDF2 expression and its downstream targets (m6A-gch1 and m6A-sting1).
  • Examined gene co-expression patterns related to YTHDF2 and PCD.

Main Results:

  • BHPF was detected in 14% of pregnant participant serum samples.
  • BHPF exposure in zebrafish caused tissue-specific PCD, leading to cardiac, vascular, and caudal vein plexus defects.
  • BHPF downregulated YTHDF2, affecting cardiomyocyte ferroptosis via gch1 translation and caudal vein plexus apoptosis via sting1 decay.
  • Distinct YTHDF2-mediated m6A regulations and co-expression patterns contributed to tissue-specific PCD.

Conclusions:

  • BHPF exposure induces tissue-specific PCD by downregulating the m6A reader YTHDF2.
  • This study uncovers a novel layer of PCD regulation involving YTHDF2-mediated m6A modifications.
  • BHPF poses a potential health threat, particularly to pregnant individuals and developing organisms, as evidenced by conserved mechanisms in mammals.
Keywords:
RNA m6A modificationbifurcation role of YTHDF2environmental stress and m6A regulationfluorene-9-bisphenol (BHPF)programmed cell deaths

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

8.6K
Use of LysoTracker to Detect Programmed Cell Death in Embryos and Differentiating Embryonic Stem Cells12:44

Use of LysoTracker to Detect Programmed Cell Death in Embryos and Differentiating Embryonic Stem Cells

Published on: October 11, 2012

23.4K

Related Concept Videos

Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.3K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.6K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.4K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K