Strategic localization of heart mitochondrial NOS: a review of the evidence.

Heart mitochondria play a central role in cell energy provision and in signaling. Nitric oxide (NO) is a free radical with primary regulatory functions in the heart and involved in a broad array of key processes in cardiac metabolism. Specific NO synthase (NOS) isoforms are confined to distinct locations in cardiomyocytes.

Alteration of rat hippocampal neurogenesis and neuronal nitric oxide synthase expression upon prenatal exposure to tamoxifen.

The present study delineates the effect of tamoxifen on neuronal density and expression of neuronal nitric oxide synthase (nNOS) in hippocampal nerve cells during prenatal and postnatal periods in rats. Pregnant rats were administered with tamoxifen one day prior to labor (E21) and on the childbirth day (E22). Hippocampi of embryos at E22 and newborns at postnatal days of 1, 7, and 21 (P1, P7, and P21) were investigated.

Importance of cytochrome c redox state for ceramide-induced apoptosis of human mammary adenocarcinoma cells.

Background: Ceramides are intracellular lipid mediator implicated in various cellular responses, including oxidative stress and programmed cell death. Studies demonstrated strong links between ceramide and the mitochondria in the regulation of apoptosis. However, the mechanism of apoptosis induced by ceramides is not fully understood.

Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells.

Overexpression of alpha-synuclein and oxidative stress has been implicated in the neuronal cell death in Parkinson's disease. Alpha-synuclein associates with mitochondria and excessive accumulation of alpha-synuclein causes impairment of mitochondrial functions. However, the mechanism of mitochondrial impairment caused by alpha-synuclein is not fully understood.

Annual International Geographic Medicine Congress Meetings in Shiraz, Iran: Publication Rates during 1999-2006.

The present study aimed to examine which portion of abstracts presented between 1999 to 2006 at Annual International Geographic Medicine Congress meetings in Shiraz, Iran, were published during 1999-2006, and to identify factors affecting publication rate of those abstracts. Two hundred fifty abstracts were reviewed and categorized according to the type of presentation, study design, sample size, main findings, source of funding, and statistical significance of the results. Principal investigators of those abstracts were provided with a questionnaire inquiring whether their abstracts lead to full-length publications in peer-reviewed journals indexed under PubMed.

Patient sources for drug information in Iran: a questionnaire-based survey.

Objectives: To identify sources used by patients to obtain drug-related information and to find which portion of patients study the Patient Information Leaflet (PIL).

Methods: A cluster random sampling was used to select 19 community pharmacies in Shiraz, Iran, from 192 pharmacies registered by Food and Drug Office of Shiraz University of Medical Sciences. Using a questionnaire, an independent assessor surveyed outpatients immediately after their prescriptions were dispensed.

mAtNOS1 induces apoptosis of human mammary adenocarcinoma cells.

mAtNOS1 is a novel gene recently reported in mammalian genome with functions that are not fully understood. The present study shows that in human mammary adenocarcinoma MCF-7 cells, mAtNOS1 expression increases mitochondrial nitric oxide and calcium. Our study further shows that overexpression of mAtNOS1 induces apoptosis in MCF-7 cells by increasing mitochondrial protein tyrosine nitration and cytochrome c release.

Detection assays for determination of mitochondrial nitric oxide synthase activity; advantages and limitations.

Nitric oxide (NO) is a reactive radical synthesized by members of the NO synthase (NOS) family, including mitochondrial-specific NOS (mtNOS). Some of the assays used for the determination of cytoplasmic NOS activity have been utilized to detect mtNOS activity. However, it seems that many of those assays need to be adjusted and optimized to detect NO in the unique environment of mitochondria.

Nitric oxide irreversibly inhibits cytochrome oxidase at low oxygen concentrations: evidence for inverse oxygen concentration-dependent peroxynitrite formation.

The present study shows that nitric oxide (NO) irreversibly inhibits purified cytochrome oxidase in a reverse oxygen concentration-dependent manner. The inhibition is dramatically protected by a peroxynitrite scavenger, suggesting that peroxynitrite is formed from the reaction of NO with cytochrome oxidase at low oxygen concentration, and that peroxynitrite is involved in irreversible cytochrome oxidase inactivation. Production of nitroxyl anion or superoxide was tested as potential mechanisms underlying the conversion of NO to peroxynitrite.

mAtNOS1 regulates mitochondrial functions and apoptosis of human neuroblastoma cells.

mAtNOS1 is a novel gene recently reported in mammalian cells with functions that are not fully understood. The present study generated human neuroblastoma SHSY cells over- and underexpressing mAtNOS1 and shows that mAtNOS1 is involved in regulating mitochondrial nitric oxide, mitochondrial transmembrane potential, protein tyrosine nitration, cytochrome c release, and apoptosis of those cells.

Significance of mitochondrial calcium and nitric oxide for apoptosis of human breast cancer cells induced by tamoxifen and etoposide.

In the present study, we tested the significance of mitochondria for apoptosis upon exposure to tamoxifen and etoposide using two human breast cancer cell lines, MCF-7 and MDA-MB-231. We showed that both tamoxifen and etoposide induced apoptosis, increased intramitochondrial calcium and nitric oxide, and decreased mitochondrial transmembrane potential in both cell lines. Both drugs increased mitochondrial protein tyrosine nitration and caused release of cytochrome c from the mitochondria of both cell lines.

Inactivation of mitochondrial respiratory chain complex I leads mitochondrial nitric oxide synthase to become pro-oxidative.

We recently demonstrated that mitochondrial nitric oxide synthase (mtNOS) functionally couples with mitochondrial respiratory chain complex I to produce nitric oxide [M.S. Parihar, R.

Association of mitochondrial nitric oxide synthase activity with respiratory chain complex I.

The present study shows that rat liver and brain mitochondrial nitric oxide synthase (mtNOS) are functionally associated with mitochondrial respiratory chain complex I. When complex I is activated, mtNOS exerts high activity and generates nitric oxide, whereas inactivation of complex I leads mtNOS to abandon its NOS activity. Functional association of mtNOS with complex I is potentially important in regulating mtNOS activity and mitochondrial functions.

Mitochondria in multiple sclerosis.

Multiple sclerosis (MS) is a neurological disorder of the central nervous system characterized by demyelination and neurodegeneration. Although the pathogenesis of MS is not completely understood, various studies suggest that immune-mediated loss of myelin and mitochondrial dysfunction are associated with the disease. Mitochondria are one of the main cellular sources of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and play a pivotal role in many neuro-pathological conditions.

12(S)-hydroperoxyeicosatetraenoic acid (12-HETE) increases mitochondrial nitric oxide by increasing intramitochondrial calcium.

12(S)-hydroxyeicosatetraenoic acid (12-HETE) is one of the metabolites of arachidonic acid involved in pathological conditions associated with mitochondria and oxidative stress. The present study tested effects of 12-HETE on mitochondrial functions. In isolated rat heart mitochondria, 12-HETE increases intramitochondrial ionized calcium concentration that stimulates mitochondrial nitric oxide (NO) synthase (mtNOS) activity.

Effect of short-term ketogenic diet on redox status of human blood.

The present study investigated the effect of a ketogenic diet on the blood redox status of healthy female subjects. Twenty healthy females with mean body mass index of 21.45 +/- 2.

Hypoxia/reoxygenation of isolated rat heart mitochondria causes cytochrome c release and oxidative stress; evidence for involvement of mitochondrial nitric oxide synthase.

The objective of the present study was to delineate the molecular mechanisms for mitochondrial contribution to oxidative stress induced by hypoxia and reoxygenation in the heart. The present study introduces a novel model allowing real-time study of mitochondria under hypoxia and reoxygenation, and describes the significance of intramitochondrial calcium homeostasis and mitochondrial nitric oxide synthase (mtNOS) for oxidative stress. The present study shows that incubating isolated rat heart mitochondria under hypoxia followed by reoxygenation, but not hypoxia per se, causes cytochrome c release from the mitochondria, oxidative modification of mitochondrial lipids and proteins, and inactivation of mitochondrial enzymes susceptible to inactivation by peroxynitrite.

Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase.

Tamoxifen is an anticancer drug that induces oxidative stress and apoptosis via mitochondria-dependent and nitric oxide (NO)-dependent pathways. The present report shows that tamoxifen increases intramitochondrial ionized Ca(2+) concentration and stimulates mitochondrial NO synthase (mtNOS) activity in the mitochondria from rat liver and human breast cancer MCF-7 cells. By stimulating mtNOS, tamoxifen hampers mitochondrial respiration, releases cytochrome c, elevates mitochondrial lipid peroxidation, increases protein tyrosine nitration of certain mitochondrial proteins, decreases the catalytic activity of succinyl-CoA:3-oxoacid CoA-transferase, and induces aggregation of mitochondria.

Mitochondrial nitric oxide synthase.

Nitric oxide (NO) regulates several cellular functions via reversible regulation of mitochondrial respiration. Nitric oxide also reacts with mitochondrial superoxide anion to produce the potent oxidative species peroxynitrite that irreversibly hinders mitochondrial activities. Recent findings demonstrating that mitochondria produce NO via mitochondrial NO synthase (mtNOS) has intrigued several laboratories revealing crucial roles for mtNOS-derived NO and peroxynitrite in regulating the functions of mitochondria, cells and organs.

Mitochondrial cytochrome c reacts with nitric oxide via S-nitrosation.

The present study demonstrates that mitochondrial cytochrome c reacts with the thiol-reacting agent N-ethylmaleimide (NEM) to produce a one NEM-adducted cytochrome c. Mitochondrial cytochrome c also reacts with 5,5'-dithio-bis-(2-nitrobenzoic acid) and 1-chloro-2,4-dinitrobenzene in a manner prevented with NEM or iodoacetic acid (IAA). NEM-treated cytochrome c has lower reducibility and lower function to support mitochondrial oxygen consumption.

Mammalian mitochondrial nitric oxide synthase: characterization of a novel candidate.

Recently a novel family of putative nitric oxide synthases, with AtNOS1, the plant member implicated in NO production, has been described. Here we present experimental evidence that a mammalian ortholog of AtNOS1 protein functions in the cellular context of mitochondria. The expression data suggest that a candidate for mammalian mitochondrial nitric oxide synthase contributes to multiple physiological processes during embryogenesis, which may include roles in liver haematopoesis and bone development.

Determination of mitochondrial nitric oxide synthase activity.

The main biological targets of nitric oxide (NO) are hemoproteins, thiols, and superoxide anion (O2-). Mitochondria possess several hemoproteins, thiol-containing molecules, and they are one of the prime cellular producers of O2-. Thus, these organelles remain one of the main biological targets for NO.

Peroxynitrite in the pathogenesis of Parkinson's disease and the neuroprotective role of metallothioneins.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra zona compacta and in other subcortical nuclei associated with a widespread occurrence of Lewy bodies. The causes of cell death in Parkinson's disease are still poorly understood, but a defect in mitochondrial oxidative phosphorylation and enhanced oxidative stress has been proposed. We have examined 3-morpholinosydnonimine (SIN-1)-induced apoptosis in control and metallothionein-overexpressing dopaminergic neurons, with a primary objective to determine the neuroprotective potential of metallothionein (MT) against peroxynitrite-induced neurodegeneration in PD.

Mitochondrial nitric oxide synthase.

Mitochondria produce nitric oxide (NO) through a Ca(2+)-sensitive mitochondrial NO synthase (mtNOS). The NO produced by mtNOS regulates mitochondrial oxygen consumption and transmembrane potential via a reversible reaction with cytochrome c oxidase. The reaction of this NO with superoxide anion yields peroxynitrite, which irreversibly modifies susceptible targets within mitochondria and induces oxidative and/or nitrative stress.