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Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study.

Imani S, Panahi Y, Salimian J, Fu J, Ghanei M - Iran J Basic Med Sci (2015)

Bottom Line: It seems SM can induce the epigenetic modifications that are translated into change in gene expression.Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients.In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD) and compared with mustard lung.

View Article: PubMed Central - PubMed

Affiliation: Systems Biology Institute, Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

ABSTRACT
Sulfur mustard (SM, bis- (2-chloroethyl) sulphide) is a chemical warfare agent that causes DNA alkylation, protein modification and membrane damage. SM can trigger several molecular pathways involved in inflammation and oxidative stress, which cause cell necrosis and apoptosis, and loss of cells integrity and function. Epigenetic regulation of gene expression is a growing research topic and is addressed by DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs expression. It seems SM can induce the epigenetic modifications that are translated into change in gene expression. Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients. In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD) and compared with mustard lung.

No MeSH data available.


Related in: MedlinePlus

DNA cross-linking by sulfur mustard
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Figure 1: DNA cross-linking by sulfur mustard

Mentions: Sulfur mustard, bis (2-chloroethyl) sulfide, (SM), is a lethal chemical warfare agent (CWA), with high absorbance and alkylating potential that can affect tissues such as the lungs, eyes and skin. Also, it can be distributed through blood and systemically affect other tissues and organs, especially liver, brain, spleen, platelets, kidney, and white and red blood cells, (1). SM can directly interact with DNA bases including 7- (2-hydroxyethylthioethyl) guanine (7-HETE-G) (2), position 3 of adenine and O6 position of guanine (3) (Figure 1). Several repair pathways including poly (ADP-ribose) polymerase (PARP) pathway, base excision repair, nucleotide excision repair, non-homologous and joining are activated following SM exposure (4). SM exposure activates PARP pathway indicating its direct/indirect genotoxic effect, and also activates the intracellular repair system. Simultaneously, accumulation of p53 could block cell cycle and provide a time for up-regulation of repair proteins such as DNA polymerase b, stimulating of base excision repair (BER). After binding to DNA, PARP-1 synthesizes a poly (ADP-ribose)chain that is recruitment signals for other repair enzymes (5). Currently, it is proposed that PARP may be a switcher between apoptosis and necrosis (6), and may have regulatory function over apoptosis (7). If damage is not repairable, apoptosis will be followed and PARP will be cleaved. But if cell misses its energy sources due to high ATP consumption of repairing system, necrosis will occur (8). Severe ATP depletion blocks cleavage of PARP by caspase-3 that leads to continuous activity of PARP (9).


Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study.

Imani S, Panahi Y, Salimian J, Fu J, Ghanei M - Iran J Basic Med Sci (2015)

DNA cross-linking by sulfur mustard
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4633454&req=5

Figure 1: DNA cross-linking by sulfur mustard
Mentions: Sulfur mustard, bis (2-chloroethyl) sulfide, (SM), is a lethal chemical warfare agent (CWA), with high absorbance and alkylating potential that can affect tissues such as the lungs, eyes and skin. Also, it can be distributed through blood and systemically affect other tissues and organs, especially liver, brain, spleen, platelets, kidney, and white and red blood cells, (1). SM can directly interact with DNA bases including 7- (2-hydroxyethylthioethyl) guanine (7-HETE-G) (2), position 3 of adenine and O6 position of guanine (3) (Figure 1). Several repair pathways including poly (ADP-ribose) polymerase (PARP) pathway, base excision repair, nucleotide excision repair, non-homologous and joining are activated following SM exposure (4). SM exposure activates PARP pathway indicating its direct/indirect genotoxic effect, and also activates the intracellular repair system. Simultaneously, accumulation of p53 could block cell cycle and provide a time for up-regulation of repair proteins such as DNA polymerase b, stimulating of base excision repair (BER). After binding to DNA, PARP-1 synthesizes a poly (ADP-ribose)chain that is recruitment signals for other repair enzymes (5). Currently, it is proposed that PARP may be a switcher between apoptosis and necrosis (6), and may have regulatory function over apoptosis (7). If damage is not repairable, apoptosis will be followed and PARP will be cleaved. But if cell misses its energy sources due to high ATP consumption of repairing system, necrosis will occur (8). Severe ATP depletion blocks cleavage of PARP by caspase-3 that leads to continuous activity of PARP (9).

Bottom Line: It seems SM can induce the epigenetic modifications that are translated into change in gene expression.Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients.In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD) and compared with mustard lung.

View Article: PubMed Central - PubMed

Affiliation: Systems Biology Institute, Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

ABSTRACT
Sulfur mustard (SM, bis- (2-chloroethyl) sulphide) is a chemical warfare agent that causes DNA alkylation, protein modification and membrane damage. SM can trigger several molecular pathways involved in inflammation and oxidative stress, which cause cell necrosis and apoptosis, and loss of cells integrity and function. Epigenetic regulation of gene expression is a growing research topic and is addressed by DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs expression. It seems SM can induce the epigenetic modifications that are translated into change in gene expression. Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients. In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD) and compared with mustard lung.

No MeSH data available.


Related in: MedlinePlus