Polyamine-dependent gene expression

Childs, April C.; Mehta, Dipti Jhewerchand; Gerner, Eugene W.

doi:10.1007/s00018-003-2332-4

Cited by 337 publications

(266 citation statements)

References 109 publications

Supporting

Mentioning

246

Contrasting

Unclassified

Order By: Relevance

“…Polyamines influence gene expression in part by regulating chromatin conformation, and polyamine depletion may affect the cellular response to HDAC inhibitors through changes in gene expression (11). Additionally, ODC is induced in response to some death signals, and polyamines regulate apoptosis by modulating the activation or expression of several apoptotic proteins (39).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ornithine decarboxylase activity in tumor cell lines correlates with sensitivity to cell death induced by histone deacetylase inhibitors

Saunders

Verdin

2006

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Inhibitors of histone deacetylases (HDAC) show significant promise as targeted anticancer agents against a variety of hematologic and solid tumors. HDAC inhibitors arrest the growth of primary cells, but they induce apoptosis or differentiation of tumor cells. Although the precise mechanism is unknown, differences in cell cycle checkpoints and chromatin structure may be responsible. Cellular polyamines regulate both cell cycle progression and chromatin structure. In tumors, polyamines are abundantly produced because of increased activity of the rate-limiting enzyme in polyamine synthesis, ornithine decarboxylase (ODC). To determine if polyamines contribute to the cellular response to HDAC inhibitors, we inhibited ODC activity with A-difluoromethylornithine. Polyamine depletion increased resistance to apoptosis induced by HDAC inhibitors. In addition, we found that ODC activity levels correlated with sensitivity to HDAC inhibitors in a panel of tumor cell lines. We conclude that polyamines participate in the cellular response to HDAC inhibitors and that ODC activity correlates with sensitivity to HDAC inhibitor -induced apoptosis. Thus, elevated polyamine levels might be a biomarker for tumor sensitivity to HDAC inhibitor -induced apoptosis. These findings warrant clinical evaluation of tumor samples to determine if high ODC activity levels predict sensitivity to HDAC inhibitors.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Polyamines (putrescine, spermidine, and spermine) are abundant cations that bind and alter the conformation and action of nucleic acids and proteins (11). Because polyamines regulate both cell cycle progression and chromatin structure, they might play a role in the cellular response to HDAC inhibitors (12).…”

Section: Introductionmentioning

confidence: 99%

Ornithine decarboxylase activity in tumor cell lines correlates with sensitivity to cell death induced by histone deacetylase inhibitors

Saunders

Verdin

2006

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…16 Nevertheless, and despite the fact that the spatial molecular arrangement in between their positive charges fits perfectly with that in between phosphates in the DNA molecule, suggesting a perfect interaction fit, spermine was shown to bind poorly to DNA, resulting in no DNA protection against nuclease degradation. 17 DNA binding by the condensing agent can be improved either by increasing the charge density of the positively charged molecule or by introducing hydrophobic contributions.…”

Section: Introductionmentioning

confidence: 99%

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

et al. 2009

View full text Add to dashboard Cite

The lack of efficient in vivo gene delivery is a well-known shortcoming of nonviral delivery vectors, in particular of chemical vectors. We developed a series of novel nonviral carriers for plasmid-based in vivo gene delivery. This new transport device is based on the assembly of DNA plasmids with synthetic derivatives of naturally occurring moleculesfatty acid-spermine conjugates (or lipospermines). We tested the ability of these fatty acid conjugates to interact with plasmid DNA (pDNA) and found that they formed DNA nanocomplexes, which are protected from DNase I degradation. This protection was shown to directly correlate with the length of the aliphatic component. However, this increase in the length of the hydrocarbon chain resulted in increased toxicity. The cationic lipids used for transfection typically have a C 16 and C 18 hydrocarbon chain. Interestingly, toxicity studies, together with further characterization studies, suggested that the two most suitable candidates for in vivo delivery are those with the shortest hydrocarbon chain, butanoyl-and decanoylspermine. Morphological characterization of DNA nanocomplexes resulting from these lipospermines showed the formation of a homogenous population, with the diameter ranging approximately from 40 to 200 nm. Butanoylspermine was found to be the most promising carrier from this series, resulting in a significantly increased gene expression, in relation to naked plasmid, in both tissues herein targeted (dermis and M. tibialis anterior). Thus, we established a correlation between the in vitro properties of the ensuing DNA nanocarriers and their efficient in vivo gene expression.

show abstract

“…Polyamines interact extensively with nucleic acids and consequently have a significant role in DNA replication, transcription, and translation (9,16,29). Intracellular polyamines in bacteria are derived both from de novo synthesis from amino acids and from the environment.…”

mentioning

confidence: 99%

Immunization with Polyamine Transport Protein PotD Protects Mice against Systemic Infection with Streptococcus pneumoniae

Shah

Swiatlo

2006

Infect Immun

View full text Add to dashboard Cite

The human pathogen Streptococcus pneumoniae contains genes for a putative polyamine ABC transporter which are organized in an operon and designated potABCD. Polyamine transport protein D (PotD) is an extracellular protein which binds polyamines and possibly other structurally related molecules. PotD has been shown to contribute to virulence in both a murine sepsis model and a pneumonia model with capsular type 3 pneumococci. The protective efficacy of recombinant PotD was evaluated by active immunization and intravenous challenge with capsular type 3 pneumococci in CBA/N mice. Immunized mice had 91.7% survival following lethal pneumococcal challenge, compared with 100% mortality in the control group. Immunized animals had high-titer anti-PotD antibodies following three immunizations with alum. Protection in a sepsis model was also seen after passive administration of rabbit antiserum raised against PotD (P < 0.004). These results suggest that antibodies to PotD confer protection against invasive pneumococcal disease and that this protein should be studied further as a potential vaccine candidate for protection against invasive pneumococcal infections.

show abstract

Polyamine-dependent gene expression

Cited by 337 publications

References 109 publications

Ornithine decarboxylase activity in tumor cell lines correlates with sensitivity to cell death induced by histone deacetylase inhibitors

Ornithine decarboxylase activity in tumor cell lines correlates with sensitivity to cell death induced by histone deacetylase inhibitors

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

Immunization with Polyamine Transport Protein PotD Protects Mice against Systemic Infection with Streptococcus pneumoniae

Contact Info

Product

Resources

About