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Cyclo(phenylalanine-proline) induces DNA damage in mammalian cells via reactive oxygen species.

ABSTRACT: Cyclo(phenylalanine-proline) is produced by various organisms such as animals, plants, bacteria and fungi. It has diverse biological functions including anti-fungal activity, anti-bacterial activity and molecular signalling. However, a few studies have demonstrated the effect of cyclo(phenylalanine-proline) on the mammalian cellular processes, such as cell growth and apoptosis. In this study, we investigated whether cyclo(phenylalanine-proline) affects cellular responses associated with DNA damage in mammalian cells. We found that treatment of 1 mM cyclo(phenylalanine-proline) induces phosphorylation of H2AX (S139) through ATM-CHK2 activation as well as DNA double strand breaks. Gene expression analysis revealed that a subset of genes related to regulation of reactive oxygen species (ROS) scavenging and production is suppressed by the cyclo(phenylalanine-proline) treatment. We also found that cyclo(phenylalanine-proline) treatment induces perturbation of the mitochondrial membrane, resulting in increased ROS, especially superoxide, production. Collectively, our study suggests that cyclo(phenylalanine-proline) treatment induces DNA damage via elevation of ROS in mammalian cells. Our findings may help explain the mechanism underlying the bacterial infection-induced activation of DNA damage response in host mammalian cells.

SUBMITTER: Lee K

PROVIDER: S-EPMC4687708 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Cyclo(phenylalanine-proline) induces DNA damage in mammalian cells via reactive oxygen species.

Lee Kwanghyun K Jeong Jae Eun JE Kim In Hwang IH Kim Kun-Soo KS Ju Bong-Gun BG

Journal of cellular and molecular medicine 20150928 12

Cyclo(phenylalanine-proline) is produced by various organisms such as animals, plants, bacteria and fungi. It has diverse biological functions including anti-fungal activity, anti-bacterial activity and molecular signalling. However, a few studies have demonstrated the effect of cyclo(phenylalanine-proline) on the mammalian cellular processes, such as cell growth and apoptosis. In this study, we investigated whether cyclo(phenylalanine-proline) affects cellular responses associated with DNA dama ...[more]

PMID: 26416514

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Project description:BackgroundBiofuels offer a viable alternative to petroleum-based fuel. However, current methods are not sufficient and the technology required in order to use lignocellulosic biomass as a fermentation substrate faces several challenges. One challenge is the need for a robust fermentative microorganism that can tolerate the inhibitors present during lignocellulosic fermentation. These inhibitors include the furan aldehyde, furfural, which is released as a byproduct of pentose dehydration during the weak acid pretreatment of lignocellulose. In order to survive in the presence of furfural, yeast cells need not only to reduce furfural to the less toxic furan methanol, but also to protect themselves and repair any damage caused by the furfural. Since furfural tolerance in yeast requires a functional pentose phosphate pathway (PPP), and the PPP is associated with reactive oxygen species (ROS) tolerance, we decided to investigate whether or not furfural induces ROS and its related cellular damage in yeast.ResultsWe demonstrated that furfural induces the accumulation of ROS in Saccharomyces cerevisiae. In addition, furfural was shown to cause cellular damage that is consistent with ROS accumulation in cells which includes damage to mitochondria and vacuole membranes, the actin cytoskeleton and nuclear chromatin. The furfural-induced damage is less severe when yeast are grown in a furfural concentration (25 mM) that allows for eventual growth after an extended lag compared to a concentration of furfural (50 mM) that prevents growth.ConclusionThese data suggest that when yeast cells encounter the inhibitor furfural, they not only need to reduce furfural into furan methanol but also to protect themselves from the cellular effects of furfural and repair any damage caused. The reduced cellular damage seen at 25 mM furfural compared to 50 mM furfural may be linked to the observation that at 25 mM furfural yeast were able to exit the furfural-induced lag phase and resume growth. Understanding the cellular effects of furfural will help direct future strain development to engineer strains capable of tolerating or remediating ROS and the effects of ROS.

Dataset Information

Cyclo(phenylalanine-proline) induces DNA damage in mammalian cells via reactive oxygen species.

Publications

Cyclo(phenylalanine-proline) induces DNA damage in mammalian cells via reactive oxygen species.

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