Mitochondrial (Mt)Dna Changes in Tissue May Not be Reflected by Depletion of Mtdna in Peripheral Blood Mononuclear Cells in HIV-Infected Patients

Antiviral Therapy - Tập 11 Số 5 - Trang 601-608 - 2006
Anne Maagaard1,2, Mona Holberg‐Petersen3, Gittan Kollberg4, Anders Oldfors4, Leiv Sandvik5,2, Johan N. Bruun1,2
1Department of Infectious Diseases, Ullevaal University Hospital, Oslo, Norway
2Faculty Division, University of Oslo, Oslo, Norway
3Department of Microbiology, Ullevaal University Hospital, Oslo, Norway
4Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden
5Center for Clinical Research, Ullevaal University Hospital, Oslo, Norway

Tóm tắt

Objectives Most data on mitochondrial toxicity have been derived from peripheral blood mononuclear cells (PBMCs). However, whether mitochondrial DNA (mtDNA) content in PBMCs reflects the mitochondrial state in tissues remains elusive. We report herein on mitochondrial toxicity in skeletal muscle in HIV-infected patients naive to antiretroviral treatment (ART [HIV+ART-naive]; n=10) patients exposed to nucleoside reverse transcriptase inhibitors (NRTIs [HIV+NRTI+]; n=24) and healthy controls ( n=11), and compare these tissue data with mtDNA in PBMCs. Methods Muscle biopsies were examined for (i) mtDNA and nuclear DNA (nDNA) content using TaqMan realtime PCR system, (ii) mtDNA deletions using long expand PCR with subsequent gel electrophoresis, and (iii) mitochondrial myopathy expressed as cytochrome c oxidase (COX)-deficient muscle fibres. Results The mt/n DNA ratio in muscle from HIV+NRTI+patients was reduced compared with HIV-negative controls ( P=0.028). Moreover, mtDNA deletions were more frequent in HIV+NRTI+ patients than in both HIV-negative controls ( P=0.009) and HIV+ART-naive patients ( P=0.005). HIV+NRTI+ also tended to have more COX-deficient fibres than HIV-negative controls ( P=0.076). COX-deficient fibres were positively correlated with mtDNA deletions in HIV+NRTI+ patients (r=0.83, P<0.001). Patients with current use of didanosine (ddI) had more frequent mtDNA deletions and COX-deficient fibres than HIV+NRTI+ not on current treatment with ddI. It should be noted that mitochondrial alterations were not correlated with mtDNA/cell in PBMCs in any group. Conclusions In skeletal muscle, HIV+NRTI+ had a reduced mt/n DNA ratio, more frequent mtDNA deletions and possibly more COX-deficient muscle fibres than HIV-negative controls. However, the mtDNA/cell in peripheral blood was decreased in both HIV+NRTI+ and HIV+ART-naive patients. Thus, mtDNA in peripheral blood may not be a relevant marker of mitochondrial toxicity in organ-specific tissue.

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Antiviral Therapy

Tập 11 Số 5

601-608

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