Is bcl-2 a Key Molecule in the Abnormal Immune Response of Hemodialysis Patients?

Martín‐Malo, Alejandro; Ramı́rez, Rafael; Aljama, Pedro

doi:10.1159/000097076

Cited by 1 publication

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“…Expression of this gene in cells has been shown to contribute to reduced cell apoptosis under cytotoxic conditions. Reports regarding the effect of HD on Bcl-2 are controversial [35]. Gene expression levels of the analyzed Bcl-2 and Bcl-2L2 in our study achieved no significant increase during the HD treatment.…”

Section: Discussioncontrasting

confidence: 63%

Acute Effects of Haemodialysis on Pro-/Anti- Apoptotic Genes in Peripheral Blood Leukocytes

Friedrich¹,

Janessa²,

Schmieder³

et al. 2008

Cell Physiol Biochem

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Several studies have implicated a remarkable dysfunctional apoptotic state and/or response in ESRD patients. Previously published studies are controversial with respect to acute effects of haemodialysis (HD) treatment on up- or downregulation of apoptotic genes. Twenty-eight chronic HD patients were haemodialysed for 4 hours with a 4008 dialyser using high-flux membranes. For subgroup analysis, patients were separated into a low (up to 0.5 mg/dl) and a high (0.5 to 5.0 mg/dl) CRP group. Blood was drawn prior to HD and 240 min after initiation of HD. Acute changes of transcript levels encoding pro- or anti-apoptotic genes were analyzed in RNA immediately isolated from blood leukocytes using quantitative real-time PCR. In the present study, we detected a significant elevation of the death receptor CD95/Fas (induction factor (IF) 1.55 ± 0.16), the death receptor 5 (DR5) (IF 1.17 ± 0.08), and caspase 8 (IF 1.37 ± 0.14) gene expression during HD. mRNA levels of the respective ligands (CD95L, TRAIL), of the caspase 5 and anti-apoptotic Bcl-2 family members such as Bcl-2 and Bcl2l2 were slightly, but not significantly, increased after HD treatment. An additional anti-apoptotic molecule, BAG3, was found to be slightly, but significantly, induced after HD (IF 1.16 ± 0.07). In addition to being an activator of immune cells, CD40L has been shown to be strongly induced after HD treatment (IF 1.70 ± 0.20). Subgroup analysis revealed no significant differences between low vs. high CRP patient groups or diabetic vs. non-diabetic patients. These results indicate a marked influence of routine haemodialysis treatment on the transcription of pro- and anti-apoptotic molecules and the involvement of the extrinsic pathway for apoptosis through the activation of death receptors and the initiator caspase 8. Furthermore, following dialysis, lymphocytes seem to be activated by CD40L, which represents an early T-cell activation marker.

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Section: Discussioncontrasting

confidence: 63%