Arsenic-induced suppression of kidney cell proliferation and the transcriptional coregulator MAML1

A Pournara1, T Holmlund, Y Lu

  • 1Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden. Annika.Wallberg@ki.se.

Insights

Mastermind-like 1 (MAML1) acts as a cell proliferation marker. Arsenic exposure reduces MAML1 levels and inhibits kidney cell proliferation, suggesting MAML1

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Toxicology

Background:

  • Mastermind-like 1 (MAML1) is a transcriptional coregulator involved in multiple signaling pathways.
  • Its role in pathways linked to cell proliferation suggests MAML1 may function as a cell proliferation marker.

Purpose of the Study:

  • To investigate the role of MAML1 as a cell proliferation marker in kidney cells.
  • To determine the effect of inorganic arsenic (arsenite) on MAML1 expression and cell proliferation.

Main Methods:

  • In silico correlation analysis of MAML1 expression with known proliferation markers (PCNA, CDC2, XRCC5).
  • Experimental manipulation of MAML1 levels (over-expression and siRNA downregulation) in human embryonic kidney (HEK) 293 cells.
  • Assessment of cell proliferation rates following MAML1 manipulation and arsenite exposure.

Main Results:

  • MAML1 expression correlated in silico with established cell proliferation markers in the kidney.
  • MAML1 over-expression increased HEK293 cell proliferation; MAML1 downregulation decreased it.
  • Arsenite exposure reduced MAML1 levels and inhibited HEK293 cell proliferation.

Conclusions:

  • MAML1 is a potential marker for cell proliferation in kidney cells.
  • Arsenic inhibits embryonic kidney cell proliferation, potentially by reducing MAML1 gene expression.

Related Concept Videos

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...
4.0K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
2.0K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.3K