Search results for " mito."
showing 10 items of 892 documents
Aging of the liver: Age-associated mitochondrial damage in intact hepatocytes
1996
Mitochondrial damage may be a major cause of cellular aging. So far, this hypothesis had only been tested using isolated mitochondria. The aim of this study was to investigate the involvement of mitochondria in aging using whole liver cells and not isolated mitochondria only. Using flow cytometry, we found that age is associated with a decrease in mitochondrial membrane potential (30%), an increase in mitochondrial size, and an increase in mitochondrial peroxide generation (23%). Intracellular peroxide levels were also increased. The number of mitochondria per cell and inner mitochondrial membrane mass did not change. Gluconeogenesis from glycerol or fructose (mitochondrial-independent) did…
Cardiovascular comorbidity in multiple sclerosis patients treated with mitoxantrone therapy: a cohort study
2017
Abstract Background Mitoxantrone (MX) has been used as second line therapy for aggressive multiple sclerosis (MS). Potential cardiotoxic effects of MX limit its use; a cumulative dose of up to 100 mg/m2, has been long considered relatively safe. We calculated the frequency of cardiac side effects in MS patients treated with MX. Methods We performed a cohort study including all MS patients treated with MX at the Neurological Department of the University Hospital of Palermo, Italy. Two hundred-sixty-four MS patients diagnosed according to validated criteria were included and followed-up until the end of September 2010. Patients were treated with MX as a second line therapy if they had no prev…
Neuroendocrine Regulation Of The IL-27-Dependent Immune Response In Macrophages
2013
Abstract The central nervous system has the ability for modulating immune responses, but the molecular mechanisms of such interactions are only partly understood. Interleukin-27 (IL-27) is a heterodimeric protein and structurally related to the IL-12 family of cytokines. IL-27 is composed of the subunits EBI3 and p28. The biological functions of IL-27 have been described as either anti-inflammatory or pro-inflammatory depending on the experimental models studied. In the current study, we investigated how production of Interleukin-27 (IL-27) is regulated by neuroendocrine hormones. We focused our work on the subunit p28, since EBI3 is also present in IL-35 and therefore is not a specific com…
Lysine triggers apoptosis through a NADPH oxidase-dependent mechanism in human renal tubular cells
2012
Progressive chronic kidney disease (CKD) is common in lysinuric protein intolerance (LPI), a primary inherited aminoaciduria characterized by massive Lysine excretion in urine. However, by which mechanisms Lysine may cause kidney damage to tubule cells is still not understood. This study determined whether Lysine overloading of human proximal tubular cells (HK-2) in culture enhances apoptotic cell loss and its associated mechanisms. Overloading HK-2 with Lysine levels reproducing those observed in urine of patients affected by LPI (10 mM) increased apoptosis (+30%; p < 0.01 vs.C), as well as Bax and Apaf-1 expressions (+30-50% p < 0.05), while downregulated Bcl-2 (-40% p < 0.05). Apoptosis …
PGC-1α: a master gene that is hard to master
2012
Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcriptional coactivator that favorably affects mitochondrial function. This concept is supported by an increasing amount of data including studies in PGC-1α gene-deleted mice, suggesting that PGC-1α is a rescue factor capable of boosting cell metabolism and promoting cell survival. However, this view has now been called into question by a recent study showing that adeno-associated virus-mediated PGC-1α overexpression causes overt cell degeneration in dopaminergic neurons. How is this to be understood, and can these seemingly conflicting findings tell us something about the role of PGC-1α in cell stress and in cont…
Mechanisms of C-reactive protein-induced blood-brain barrier disruption.
2009
Background and Purpose— Increased mortality after stroke is associated with brain edema formation and high plasma levels of the acute phase reactant C-reactive protein (CRP). The aim of this study was to examine whether CRP directly affects blood–brain barrier stability and to analyze the underlying signaling pathways. Methods— We used a cell coculture model of the blood–brain barrier and the guinea pig isolated whole brain preparation. Results— We could show that CRP at clinically relevant concentrations (10 to 20 μg/mL) causes a disruption of the blood–brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fcγ receptors CD16/32 fo…
Chronic heart damage following doxorubicin treatment is alleviated by lovastatin.
2014
The anticancer efficacy of anthracyclines is limited by cumulative dose-dependent early and delayed cardiotoxicity resulting in congestive heart failure. Mechanisms responsible for anthracycline-induced heart damage are controversially discussed and effective preventive measures are preferable. Here, we analyzed the influence of the lipid lowering drug lovastatin on anthracycline-induced late cardiotoxicity three month after treatment of C57BL/6 mice with five low doses of doxorubicin (5×3mg/kg BW; i.p.). Doxorubicin increased the cardiac mRNA levels of BNP, IL-6 and CTGF, while the expression of ANP remained unchanged. Lovastatin counteracted these persisting cardiac stress responses evoke…
Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance.
2009
Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial function.Our objective was to assess mitochondrial function by evaluating mitochondrial oxygen (O(2)) consumption, reactive oxygen species (ROS) production, levels of glutathione (GSH), the oxidized glutathione/GSH ratio, TNFalpha levels, and membrane potential. Additionally, we have evaluated mitochondrial complex I as a target of the oxidative stress responsible for PCOS in polymorphonuclear cells.This was a prospective controlled study conducted in an academic medical center.The study population consisted of 20 lean reproductive-age women with PCOS and 20 body composition-matched controls.…
Interleukin 12 enhances deficient HCV-antigen-induced Th1-type immune response of peripheral blood mononuclear cells
1998
The aim of this study was to examine the possible immunomodulating effects of rhIL-12 on the immune response induced by different hepatitis C virus (HCV) antigens. Freshly isolated peripheral blood mononuclear cells (PBMC) of 33 patients with chronic HCV infection were stimulated with optimal concentrations of antigens from the NS3, NS4, NS5, and core region of HCV in the absence or presence of interleukin12 (IL-12). Stimulation by α-CD3 + α-CD28, lipopolysaccharide (LPS), and pokeweed mitogen (PWM) were used as controls. Proliferation and cytokine production were determined by 3H-thymidine uptake and enzyme-linked immunosorbent assay (ELISA) after 72 hr. After stimulation with antigen or a…
POLYPHENOLS FROM RED WINE MODULATE IMMUNE RESPONSIVENESS: BIOLOGICAL AND CLINICAL SIGNIFICANCE.
2008
Many studies have been conducted on the effects of red wine polyphenols on certain diseases, primarily, coronary heart disease (CHD) and, in this respect, evidence has been demonstrated that intake of red wine is associated with a reduction of CHD symptomatology. In this framework, the purpose of this review is to illustrate the effects of polyphenols on immune cells from human healthy peripheral blood. Data will show that polyphenols are able to stimulate both innate and adaptive immune responses. In particular, the release of cytokines such as interleukin (IL)-12, interferon (IFN)-gamma, and IL-10 as well as immunoglobulins may be important for host protection in different immune related …