Gradual Changes in Permeability of Inner Mitochondrial Membrane Precede the Mitochondrial Permeability Transition

Balakirev, Maxim Y.; Zimmer, Guido

doi:10.1006/abbi.1998.0738

Cited by 23 publications

(16 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we were interested in the response of crosslinked lPEI-mediated gene transfer to changes in the reducing/ oxidizing environment of cells. To this end, 1 h before transfection, CHO-K1 cells were treated with 50 M duroquinone, an agent that oxidizes NADPH/H ϩ , thereby lowering its reducing potential (26,27) (see SI Fig. 9).…”

Section: Resultsmentioning

confidence: 99%

Breaking up the correlation between efficacy and toxicity for nonviral gene delivery

Breunig

Lungwitz

Liebl

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

405

322

View full text Add to dashboard Cite

Nonviral nucleic acid delivery to cells and tissues is considered a standard tool in life science research. However, although an ideal delivery system should have high efficacy and minimal toxicity, existing materials fall short, most of them being either too toxic or little effective. We hypothesized that disulfide cross-linked lowmolecular-weight (MW) linear poly(ethylene imine) (MW <4.6 kDa) would overcome this limitation. Investigations with these materials revealed that the extracellular high MW provided outstandingly high transfection efficacies (up to 69.62 ؎ 4.18% in HEK cells). We confirmed that the intracellular reductive degradation produced mainly nontoxic fragments (cell survival 98.69 ؎ 4.79%). When we compared the polymers in >1,400 individual experiments to seven commercial transfection reagents in seven different cell lines, we found highly superior transfection efficacies and substantially lower toxicities. This renders reductive degradation a highly promising tool for the design of new transfection materials.biodegradable ͉ polyethylenimine ͉ nucleic acid ͉ disulfide bond ͉ transfection G ene transfer into cells has become a standard procedure in life science research. Nonviral carriers have gained in importance in recent years because of their safety in handling and ease of application compared with viral vectors. Browsing databases such as PubMed or Chemical Abstracts reveals that almost every publication related to genetics, biochemistry, molecular biology, developmental biology, or neurology incorporated lipid-or polymer-based transfection as a pivotal tool for the investigation of various cellular processes. Therefore, it appears that the delivery of nucleic acids is a well established method for the transfection of mammalian cells, and, given the amount of research data that has been produced, one would assume that the procedures for nonviral transfection would be well optimized. A closer look at the contemporary literature, however, reveals that doubts seem justified. Contemporary transfection reagents are almost universally toxic because of their cationic or amphiphilic character (1-4).The dilemma that we face is exemplified by considering the polymeric transfection agent poly(ethylene imine) (PEI). Since its introduction in 1995, PEI has been considered the gold standard for polymer-based gene carriers because of the relatively high transfection efficacy of its polyplexes (complex of nucleic acid and polymer) (5, 6). However, it has been shown that both the efficacy and toxicity of PEI are strongly correlated with its molecular weight (MW) as well as its structure (branched or linear: bPEI or lPEI, respectively) (7-17). Efficacy and adverse reactions seem thereby to be strongly associated. PEI is not the only material that suffers from this ''malignant'' correlation. Nonviral transfection seems like choosing between Scylla and Charybdis: either a high transfection efficacy, which is associated with a devastating toxicity, or a low efficacy, which does not affect the cell viability at ...

show abstract

Section: Resultsmentioning

confidence: 99%

Breaking up the correlation between efficacy and toxicity for nonviral gene delivery

Breunig

Lungwitz

Liebl

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

405

322

View full text Add to dashboard Cite

show abstract

“…The possibility of glibenclamide to induce IMAC opening by depletion of matrix Mg 2+ by exchange with H + , like A23187 [15], is excluded, because glibenclamide, in contrast with A23187, did not increase the transmembrane potential ( ) of succinate-respiring mitochondria in a free-Mg 2+ reaction medium (results not shown). IMAC opening by glibenclamide may be related with its ability to induce mitochondrial matrix alkalinization [12]. This is the first study presenting evidence that glibenclamide permeabilizes the inner mitochondrial membrane to Cl − by opening IMAC.…”

Section: Discussionmentioning

confidence: 86%

“…In intact mitochondria, the electrogenic transport of potassium (K + uniport) induced by Mg 2+ depletion is also blocked by glibenclamide in a concentration-dependent manner, with an IC 50 of 20 M [11]. However, a more recent study showed that 50 M glybenclamide induced, by itself, K + influx inside mitochondria [12].…”

Section: Introductionmentioning

confidence: 99%

“…However, the mechanism by which glibenclamide interferes with mitochondrial bioenergetics is not completely understood. Some investigators reported that it may be related with the ability of glibenclamide to increase the proton conductance of the inner mitochondrial membrane [13], while others report that it may be related with K + influx inside mitochondria [12].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glibenclamide interferes with mitochondrial bioenergetics by inducing changes on membrane ion permeability

Férnandes

Santos

Moreno

et al. 2004

J Biochem & Molecular Tox

View full text Add to dashboard Cite

The interference of glibenclamide, an antidiabetic sulfonylurea, with mitochondrial bioenergetics was assessed on mitochondrial ion fluxes (H+, K+, and Cl−) by passive osmotic swelling of rat liver mitochondria in K‐acetate, KNO3, and KCl media, by O2 consumption, and by mitochondrial transmembrane potential (Δψ). Glibenclamide did not permeabilize the inner mitochondrial membrane to H+, but induced permeabilization to Cl− by opening the inner mitochondrial anion channel (IMAC). Cl− influx induced by glibenclamide facilitates K+ entry into mitochondria, thus promoting a net Cl−/K+ cotransport, Δψ dissipation, and stimulation of state 4 respiration rate. It was concluded that glibenclamide interferes with mitochondrial bioenergetics of rat liver by permeabilizing the inner mitochondrial membrane to Cl− and promoting a net Cl−/K+ cotransport inside mitochondria, without significant changes on membrane permeabilization to H+. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:162–169, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20022

show abstract

“…The opening of mitochondrial permeability transition pore is strongly associated with the dissipation of DJ m (Balakirev and Zimmer, 1998). CSA has been described as MPT inhibitor in isolated mitochondria (Nicolli et al, 1996) or in intact cells (Uchino et al, 2002) and has been used as a predictive of MPT involvement in DJ m dissipation.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporin A does not protect the disruption of the inner mitochondrial membrane potential induced by potassium ionophores in intact K562 cells

Marques‐Santos

Coqueiro²,

Rumjanek³

2006

Cell Biology International

View full text Add to dashboard Cite

Mitochondrial dysfunction has been widely associated with programmed cell death. Studies of intact cells are important for the understanding of the process of cell death and its relation to mitochondrial physiology. Using cytofluorometric approaches we studied the mitochondrial behavior in an erythroleukemic cell line. The effects of protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), potassium exchanger (nigericin), potassium ionophore (valinomycin), Na+K+-ATPase inhibitor (ouabain) and mitochondrial permeability transition pore inhibitor (cyclosporin A) were evaluated. Cyclosporin A (CSA) was very effective in attenuating the disruption of inner mitochondrial membrane potential induced by CCCP. However, CSA failed to protect the loss of inner mitochondrial membrane potential induced by potassium intracellular flux manipulation. Our findings suggest that mitochondrial cyclophilin is not involved in the cell events mediated by deregulation of potassium flux, underlining the need for further studies in intact tumor cells for a better understanding of the involvement of mitochondria physiology in cell death events.

show abstract

Gradual Changes in Permeability of Inner Mitochondrial Membrane Precede the Mitochondrial Permeability Transition

Cited by 23 publications

References 66 publications

Breaking up the correlation between efficacy and toxicity for nonviral gene delivery

Breaking up the correlation between efficacy and toxicity for nonviral gene delivery

Glibenclamide interferes with mitochondrial bioenergetics by inducing changes on membrane ion permeability

Cyclosporin A does not protect the disruption of the inner mitochondrial membrane potential induced by potassium ionophores in intact K562 cells

Contact Info

Product

Resources

About