Related Experiment Video
Updated: Aug 31, 2025
08:51
Profiling of Permethylated Mucin O-glycans Using Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry
Published on: June 20, 2025
268
Cell cycle disturbances in mucopolysaccharidoses: Transcriptomic and experimental studies on cellular models
Joanna Brokowska1, Lidia Gaffke1, Karolina Pierzynowska1
1Department of Molecular Biology, University of Gdansk, 80-308 Gdansk, Poland.
Experimental Biology and Medicine (Maywood, N.J.)
|August 24, 2022
Summary
Mucopolysaccharidoses (MPS) disrupt the cell cycle in all disease types, with common gene expression changes and altered cell phase distribution. Reducing glycosaminoglycans (GAGs) partially corrects these cell cycle defects.
Area of Science:
- Cell Biology
- Genetics
- Biochemistry
Background:
- Mucopolysaccharidoses (MPS) are lysosomal storage diseases characterized by glycosaminoglycan (GAG) accumulation.
- Cellular dysfunctions in MPS are attributed to GAG storage and secondary changes.
- The cell cycle's role in MPS pathogenesis has been under-investigated.
Purpose of the Study:
- To investigate cell cycle disturbances in various types of Mucopolysaccharidoses.
- To identify common mechanisms underlying cell cycle dysregulation in MPS.
- To explore potential therapeutic strategies targeting cell cycle abnormalities.
Main Methods:
- Transcriptomic analysis to assess gene expression related to the cell cycle.
- Flow cytometry to evaluate cell cycle phase distribution.
- Treatment of MPS fibroblasts with GAG-reducing agents.
Main Results:
- Dysregulated expression of cell cycle genes was observed across all MPS types, indicating a common mechanism.
- MPS cells exhibited altered cell cycle progression, with increased G0/G1 and decreased G2/M phases.
- Increased cyclin D1 levels and disrupted timing were implicated in the cell cycle dysregulation.
- Reduction of GAG levels partially improved cell cycle parameters in MPS fibroblasts.
Conclusions:
- Cell cycle perturbations are a hallmark of Mucopolysaccharidoses, driven by common molecular mechanisms.
- Cyclin D1 may play a significant role in MPS-associated cell cycle dysregulation.
- Combined therapeutic strategies involving GAG reduction and cyclin D1 inhibition warrant further investigation for MPS treatment.
Related Concept Videos
02:23Abnormal Proliferation
4.6K
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...
4.6K
02:39Positive Regulator Molecules
5.6K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.6K
01:27Molecular Factors Affecting Cell Division
3.3K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.3K
01:05Proteoglycans
4.0K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
4.0K
01:22Lysosomal Hydrolases
3.9K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.9K