scholarly journals Mitochondrial DNA Content, an Inaccurate Biomarker of Mitochondrial Alteration in Human Immunodeficiency Virus-Related Lipodystrophy

2008 ◽  
Vol 52 (5) ◽  
pp. 1670-1676 ◽  
Author(s):  
Min Ji Kim ◽  
Claude Jardel ◽  
Cyrille Barthélémy ◽  
Véronique Jan ◽  
Jean Philippe Bastard ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Human Immunodeficiency Virus ◽  
Mitochondrial Dna ◽  
Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Nuclear Dna ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mtdna Depletion ◽  
Immunodeficiency Virus ◽  
Mitochondrial Alteration

ABSTRACT Lipoatrophy is a prevalent side effect of antiretroviral treatment of human immunodeficiency virus (HIV) infection. Its mechanisms are still disputed but include mitochondrial toxicity and, in particular, mitochondrial DNA (mtDNA) depletion induced by nucleoside reverse transcriptase inhibitors. To obtain an integrated evaluation of the mitochondrial alteration in lipoatrophy, we investigated the DNA, RNA, and protein levels in 15 samples of abdominal subcutaneous adipose tissue from HIV-infected patients with peripheral lipoatrophy and compared the results with those for 15 samples from age- and body mass index-matched controls. The DNA and RNA analyses used PCR-based techniques, while proteins were quantified with enzyme-linked immunosorbent assay and measurement of activities with spectrophotometric assays. Depletion of mtDNA and mtDNA-encoded MT-CO2 mRNA was present, but normal levels of mtDNA-dependent activity (cytochrome c oxidase) and protein (MT-CO2p) showed that it was compensated for. An increase in nuclear-DNA-dependent mitochondrial activities (citrate synthase and malate dehydrogenase) and protein (COX4I1p), as well as transcriptional up-regulation of nuclear-DNA-encoded mitochondrial genes (COX4I1 and UCP2), demonstrated increased mitochondrial biogenesis. However, the expression of the known transcription factors of mitochondrial biogenesis (TFAM, NRF1, GABPA, PPARGC1A, PPARGC1B, and PPRC1) was normal or decreased. Increased amounts of activated caspase 3 and of DDIT3 mRNA showed the induction of apoptosis and oxidative stress, respectively. The mtDNA content did not correlate with any other mitochondrial parameter. In conclusion, mtDNA content does not appear to be an accurate biomarker of mitochondrial alteration in lipoatrophic adipose tissue. The preservation of mtDNA-dependent mitochondrial functions occurred despite severe mtDNA depletion. The presence of significant oxidative stress and apoptosis did not correlate with the mtDNA content.

scholarly journals Cytotoxicological Analysis of a gp120 Binding Aptamer with Cross-Clade Human Immunodeficiency Virus Type 1 Entry Inhibition Properties: Comparison to Conventional Antiretrovirals

2009 ◽  
Vol 53 (7) ◽  
pp. 3056-3064 ◽  
Author(s):  
Walter Rangel Lopes de Campos ◽  
Dayaneethie Coopusamy ◽  
Lynn Morris ◽  
Bongani M. Mayosi ◽  
Makobetsa Khati
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mitochondrial Dna ◽  
Reverse Transcriptase ◽  
Mononuclear Cells ◽  
Nuclear Dna ◽  
Cell Types ◽  
Reverse Transcriptase Inhibitors ◽  
Human Cardiomyocytes ◽  
Immunodeficiency Virus

ABSTRACT The long-term cumulative cytotoxicity of antiretrovirals (ARVs) is among the major causes of treatment failure in patients infected with human immunodeficiency virus (HIV) and patients with AIDS. This calls for the development of novel ARVs with less or no cytotoxicity. In the present study, we compared the cytotoxic effects of a cross-clade HIV type 1-neutralizing aptamer called B40 with those of a panel of nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), and the entry inhibitor (EI) T20 in human cardiomyocytes and peripheral blood mononuclear cells. An initial screen in which cell death was used as the end-point measurement revealed that the B40 aptamer and T20 were the only test molecules that had insignificant (0.61 < P < 0.92) effects on the viability of both cell types at the maximum concentration used. PIs were the most toxic class (0.001 < P < 0.00001), followed by NNRTIs and NRTIs (0.1 < P < 0.00001). Further studies revealed that B40 and T20 did not interfere with the cellular activity of the cytochrome P450 3A4 enzyme (0.78 < P < 0.24) or monoamine oxidases A and B (0.83 < P < 0.56) when the activities of the enzymes were compared to those in untreated controls of both cell types. Mitochondrion-initiated cellular toxicity is closely associated with the use of ARVs. Therefore, we used real-time PCR to quantify the relative ratio of mitochondrial DNA to nuclear DNA as a marker of toxicity. The levels of mitochondrial DNA remained unchanged in cells exposed to the B40 aptamer compared to the levels in untreated control cells (0.5 > P > 0.06). These data support the development of B40 and related EI aptamers as new ARVs with no cytotoxicity at the estimated potential therapeutic dose.

Relation of Subepicardial Adipose Tissue to Carotid Intima-Media Thickness in Patients With Human Immunodeficiency Virus

2007 ◽  
Vol 99 (10) ◽  
pp. 1470-1472 ◽  
Author(s):  
Gianluca Iacobellis ◽  
Adriano M. Pellicelli ◽  
Arya M. Sharma ◽  
Benvenuto Grisorio ◽  
Giorgio Barbarini ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adipose Tissue ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Media Thickness ◽  
Immunodeficiency Virus

Abstract 206: Accumulation of Mitochondrial DNA Mutations Impairs Survival, Proliferation, and Differentiation of Cardiac Progenitor Cells

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Amabel M Orogo ◽  
Dieter A Kubli ◽  
Anne N Murphy ◽  
Åsa B Gustafsson
Keyword(s):  
Mitochondrial Dna ◽  
Progenitor Cells ◽  
Mitochondrial Biogenesis ◽  
Nuclear Dna ◽  
Critical Role ◽  
Chemotherapeutic Agents ◽  
Cardiac Progenitor Cells ◽  
Mtdna Mutations ◽  
Differentiation Medium ◽  
Proliferation And Differentiation

Activation and participation of cardiac progenitor cells (CPCs) in regeneration are critical for effective repair in the wake of pathologic injury. Stem cell activation and commitment involve increased energy demand and mitochondrial biogenesis. To date, little attention has been paid to the importance of mitochondria in CPC survival, proliferation and differentiation. CPC function is reduced with age but the underlying mechanism is still unclear. Mitochondrial DNA (mtDNA) is more susceptible to oxidative attacks than nuclear DNA due to its proximity to the mitochondrial respiratory chain and lack of protective histone-like proteins. With age, mtDNA accumulates mutations that can impair mitochondrial respiration and increase ROS production. In this study, we examined the effects of accumulating mtDNA mutations on CPC proliferation and survival. We have found that incubation of uncommitted c-kit+ CPCs in differentiation medium increased mitochondrial mass and expansion of the mitochondrial network, which correlated with increased cell size and expression of cardiac lineage commitment markers. Differentiation activated mitochondrial biogenesis, increased mtDNA copy number, and enhanced oxidative capacity and cellular ATP levels in CPCs. To investigate the effect of mtDNA mutations and aging on CPC survival and function, we utilized a mouse model in which a mutation in the mtDNA polymerase γ (POLG m/m ) leads to accumulation of mtDNA mutations, mitochondrial dysfunction, and accelerated aging. Isolated CPCs from hearts of 2-month old POLG m/m mice had reduced proliferation and were more susceptible to oxidative stress and chemotherapeutic agents compared to WT CPCs. The majority of POLG m/m CPCs contained fragmented mitochondria as shown by immunostaining. Incubation in differentiation medium resulted in fewer GATA-4 positive POLG m/m CPCs compared to WT CPCs. The reduced differentiation in these POLG m/m CPCs correlated with reduced PGC-1α expression and OXPHOS protein levels, suggesting that mitochondrial biogenesis is impaired. These data demonstrate that mitochondria play a critical role in CPC function, and accumulation of mtDNA mutations impairs CPC function and reduces their repair potential.

scholarly journals Prevalence of Sexually Transmitted Diseases and Transmission of HIV in Dhaka, Bangladesh

2009 ◽  
Vol 3 (1) ◽  
pp. 27-33
Author(s):  
Tahmina Shirin ◽  
Saidur Rahman ◽  
Fareha Jesmin Rabbi ◽  
Md Humayun Kabir ◽  
KZ Mamun
Keyword(s):  
Human Immunodeficiency Virus ◽  
Herpes Simplex ◽  
Chlamydia Trachomatis ◽  
Sexually Transmitted Diseases ◽  
Treponema Pallidum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sexually Transmitted ◽  
Immunodeficiency Virus ◽  
Simplex Virus

The prevalence of sexually transmitted diseases (STDs) among patients attending out patients department of Skin and Venereal diseases of Dhaka Medical College Hospital, Dhaka and Shahid Sohrawardy Hospital, Dhaka was studied. A total of 230 patients were enrolled in the study during the period of July, 2006 to May, 2007. Urethral and endocervical swabs were collected from the participants for detection of Neisseria gonorrheae (by culture), Chlamydia trachomatis (by immunochromatoghraphy) and blood samples for the detection of Treponema pallidum antibody (by rapid plasma regain and Treponema pallidum haemagglutination assay), Herpes simplex virus type 2 antibody (both IgM and IgG by enzyme linked immunosorbent assay) and Human Immunodeficiency virus antibody (by enzyme linked immunosorbent assay). Socio-demographic data and data regarding high-risk sexual behavior were also collected. Out of 230 participants, 199 (86.5%) were positive for STDs pathogens studied, among them, 98 (42.6%) were infected with single pathogen and 101 (43.9%) were suffering from multiple infections. The prevalences of N. gonorrheae, C. trachomatis, T. pallidum, and HSV type 2 were 90 (39.1%), 110 (47.8%), 28 (12.2%) and 88 (38.2%) respectively. However, none of them were positive for HIV infection. Use of condom was significantly associated with protection of the participants against STDs. Keywords: Sexually Transmitted Diseases, Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Herpes simplex virus type-2, Human Immunodeficiency virus   doi: 10.3329/bjmm.v3i1.2968 Bangladesh J Med Microbiol 2009; 03 (01): 27-33

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