Enhancement of Coproporphyrinogen III Transport into Isolated Transformed Leukocyte Mitochondria by ATP

Rebeiz, Natalie; Arkins, Seán; Kelley, Keith W.; Rebeiz, Constantin A.

doi:10.1006/abbi.1996.0417

Cited by 33 publications

(21 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Biochemical characterization of parental LM3 and ALA-PDT resistant clones. - We performed also colocalization studies of endogenous PpIX coincubated with lisotracker and the benzodiazepine analogue, FGIN-1-27-NBD, which attaches to the mitochondrial benzodiazepine receptor localized in the outer mitochondrial membrane, postulated to bind porphyrins (20). No major differences among the cells were found in either case (data not shown).…”

Section: Resultsmentioning

confidence: 95%

Tumor cell lines resistant to ALA-mediated photodynamic therapy and possible tools to target surviving cells

Casas¹,

Perotti²,

Ortel³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

Abstract.We isolated and characterized cell lines resistant to aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) derived from a murine adenocarcinoma and studied cross resistance with other injuries. The most resistant clones were numbers 4 and 8, which exhibited 6.7-and 4.2-fold increase in resistance respectively. Several characteristics were altered in these clones. A 2-fold increase in cell volume, higher cell spreading, and a more fibroblastic, dendritic pattern, were the morphology features that led us to think they could have different adhesive, invasive or metastatic phenotypes. The amount of porphyrins synthesized per cell in the resistant clones was similar to the parental line but, when it was expressed per mg protein, there was a 2-fold decrease, with a higher proportion of hydrophilic porphyrins. These cells were not cross-resistant to photosensitization with Benzoporphyrin derivative and Merocyanine 540, but exhibited a slight resistance to exogenous protoporphyrin IX treatment. Both clones displayed higher protein content and increased number of mitochondria, together with a higher oxygen consumption. The distinctive features found in the resistant lines led as to think how to exploit the changes induced by PDT treatment to target surviving cells. Those hypoxic cells can be also a preferential target of bioreductive drugs and hypoxia-directed gene therapy, and would be sensitive to treatment with other photosensitizers.

show abstract

Section: Resultsmentioning

confidence: 95%

Tumor cell lines resistant to ALA-mediated photodynamic therapy and possible tools to target surviving cells

Casas¹,

Perotti²,

Ortel³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Porphyrins, in particular PpIX, are well known as ligands of the PBR (10)(11)(12). In the heme biosynthetic pathway, although coproporphyrinogen III may traverse the channel from the cytosol to the matrix (25)(26)(27)(28), the HAL-induced endogenous PpIX may also use this channel for its transportation from the matrix to the cytosol (25)(26)(27). Because the targets of PDT are the sites where the photosensitizer is localized, any sensitive biological structures associated with porphyrin transportation channel at the inner and outer mitochondrial membranes are among the targets for PDT with endogenous PpIX induced by HAL.…”

Section: Discussionmentioning

confidence: 99%

Targeting PBR by Hexaminolevulinate-Mediated Photodynamic Therapy Induces Apoptosis through Translocation of Apoptosis-Inducing Factor in Human Leukemia Cells

et al. 2005

View full text Add to dashboard Cite

Photodynamic therapy (PDT) with endogenous protoporphyrin IX derived from 5-aminolevulinic acid or its derivatives has been established for treatments of several premalignancies and malignancies; however, the mechanism of the modality is not fully elucidated. The mitochondrial permeability transition pore consists mainly of the mitochondrial outer membrane voltage-dependent anion channel and the peripheral benzodiazepine receptor (PBR) and the mitochondrial inner membrane adenine nucleotide translocator (ANT). These mitochondrial proteins are responsible for the permeability transition that leads to apoptosis. In the present study, the human leukemia cell line, Reh, was treated with PDT using hexaminolevulinate (HAL). More than 80% of apoptotic Reh cells were found after HALmediated PDT (HAL-PDT) with high-molecular-weight (50 kbp) DNA fragmentation. Addition of PK11195 or Ro5-4864, two ligands of PBR, during HAL-PDT significantly inhibited the apoptotic effect. Bongkrekic acid, a ligand for ANT, also reduced the PDT effect. Although the mitochondrial transmembrane potential collapsed, neither cytosolic translocation of mitochondrial cytochrome c nor activation of caspase-9, caspase-8, caspase-3, and poly(ADP-ribose) polymerase were found. However, nuclear translocation of mitochondrial apoptosis-inducing factor (AIF) was shown by both immunoblotting and immunocytochemistry. Because AIF is the sole one among all proapoptotic factors involved in caspase-dependent and caspase-independent pathways that induces the high-molecular-weight DNA fragmentation, we conclude that HAL-PDT specifically targets PBR, leading to apoptosis of the Reh cells through nuclear translocation of mitochondrial AIF. This study suggests PBR as a possible novel therapeutic target for HAL-based PDT of cancer. (Cancer Res 2005; 65(23): 11051-60)

show abstract

“…Porphyrins (porphyrinogens) are proposed to be endogenous ligand(s) for both TspO (1) and MBR (17)(18)(19). Therefore we examined the effect of various porphyrins and porphyrinogens on the dimerization of TspO in cells and in cell-free extracts.…”

Section: Discussionmentioning

confidence: 99%

TspO of Rhodobacter sphaeroides

Yeliseev¹,

Kaplan

2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

The function and specific structural aspects of the tryptophan-rich sensory protein (TspO) of Rhodobacter sphaeroides 2.4.1 were studied using site-directed mutagenesis involving some 17 different amino acids. The choice of these amino acids changes was dictated from an analysis of the TspO family of proteins derived from the data bases. These studies demonstrated the importance of several highly conserved tryptophan residues in the sensory transduction pathway involving TspO through the proposed binding of an intermediate(s) in the tetrapyrrole biosynthesis pathway. These studies also revealed that the substitution of one or several of the amino acid residues dramatically affected, either directly or indirectly, the levels of TspO in the membranes of R. sphaeroides. Mounting evidence is presented suggesting that TspO normally forms a dimer within the bacterial outer membrane, and the dimer form of TspO may be the active form for TspO function. Because our earlier studies provided us with a functional framework within which to view these amino acid substitutions, we are able to suggest a preliminary model for TspO structure-function. Not only do these studies tell us more about TspO, but they also shed light on the TspO homologue, the drug-binding component of the mitochondrial peripheral benzodiazepine receptor. Mounting evidence draws numerous parallelism between these proteins and supports the significance of using TspO as a model for the structure and function of the mitochondrial protein.

show abstract

Enhancement of Coproporphyrinogen III Transport into Isolated Transformed Leukocyte Mitochondria by ATP

Cited by 33 publications

References 0 publications

Tumor cell lines resistant to ALA-mediated photodynamic therapy and possible tools to target surviving cells

Tumor cell lines resistant to ALA-mediated photodynamic therapy and possible tools to target surviving cells

Targeting PBR by Hexaminolevulinate-Mediated Photodynamic Therapy Induces Apoptosis through Translocation of Apoptosis-Inducing Factor in Human Leukemia Cells

TspO of Rhodobacter sphaeroides

Contact Info

Product

Resources

About