RGD Reference Report - Regulation of porphyrin synthesis and photodynamic therapy in heavy metal intoxication. - Rat Genome Database

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Regulation of porphyrin synthesis and photodynamic therapy in heavy metal intoxication.

Authors: Grinblat, B  Pour, N  Malik, Z 
Citation: Grinblat B, etal., J Environ Pathol Toxicol Oncol. 2006;25(1-2):145-58.
RGD ID: 4144781
Pubmed: PMID:16566714   (View Abstract at PubMed)

Protoporphyrin IX (PpIX) synthesis by malignant cells is successfully exploited for photodynamic therapy (PDT) following administration of 5-aminolevulinic acid (ALA) and light irradiation. The influence of two environmental heavy metal poisons, lead and gallium, on PpIX-synthesis and ALA-PDT was studied in two neu-ronal cell lines, SH-SY5Y neuroblastoma and PC12 pheochromocytoma. The heavy metal intoxication affected two of the heme-synthesis enzymes, ALA-dehydratase (ALAD) and porphobilinogen deaminase (PBGD). The present results show that lead poisoning significantly decreased the PBGD cellular level and inhibited its enzymatic activity, whereas the effects of gallium were less prominent. Although, the protein levels were reduced, the mRNA levels of PBGD remained unchanged during metal intoxication. These findings show additional inhibitory activity of lead on top of its classical effect on ALAD. Proteasome activity was enhanced during lead treatment, as measured by the AMC fluorigenic proteasome assay. The reduction in PBGD levels was not a consequence of PBGD mRNA reduced synthesis, which remained unchanged as shown by RT-PCR analysis. As a result of the lead poisoning, marked alterations in the cell cycle were observed, including a decreased G1 phase and an increased number of S phase cells. The efficacy of ALA-PDT was reduced in correlation with decreased activities of the enzymes during lead intoxication. We may conclude that lead poisoning adversely affects the outcome of ALA photodynamic therapy of cancer.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AladRatcellular response to lead ion  IEP lead and galliumRGD 
HmbsRatcellular response to lead ion  IEP  RGD 
HmbsRatresponse to lead ion  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Alad  (aminolevulinate dehydratase)
Hmbs  (hydroxymethylbilane synthase)


Additional Information