The growing family of mitochondrial carriers in Arabidopsis.
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Arabidopsis↗
Biomedical subjects
Luigi Palmieri
Publications and source records attributed to Luigi Palmieri.
[The global cardiovascular risk chart].
BACKGROUND: Risk charts, built through risk functions deriving from longitudinal studies, are used in order to identify individuals at high risk for cardiovascular disease. For this reason the function has been identified and the global cardiovascular risk chart of the CUORE Project has been prepared, using Italian data coming from different cohorts enrolled between the '80s and the '90s, whose risk factors had been collected by standardized procedures. METHODS: The following risk factors have been used: age (10-year period, 40-49, 50-59, 60-69 years), gender (men and women), systolic blood pressure (< or = 129, 130-149, 150-169, > or = 170 mmHg), serum cholesterol (< or = 173, 174-212, 213-251, 252-290, > or = 291 mg/dl), smoking habit (yes, no) and presence of diabetes (yes, no); the first coronary or cerebrovascular event in people aged 40-69 years with no other previous cardiovascular events was considered as endpoint; survival has been assessed up to December 1998. RESULTS: Out of 18,028 people aged 40-69 years with no previous cardiovascular events, 647 first major cardiovascular events have been identified and validated, 449 coronary and 198 cerebrovascular. Charts are divided according to men and women and to diabetics and non-diabetics respectively; the different colors represent the percent level of risk and go from light green (< 5% in 10 years for men, < 1% in 5 years for women), dark green (between 5 and 10% for men, between 1 and 3% for women), yellow (between 10 and 15% for men, between 3 and 5% for women), orange (between 15 and 20% for men, between 5 and 7% for women), red (between 20 and 30% for men, between 7 and 10% for women), violet (> 30% for men, > 10% for women). CONCLUSIONS: The risk charts were built with data collected in recent years on men and women with a median follow-up of 10 years for men and 5 years for women, considering the first major fatal or non-fatal cardiovascular event as endpoint. Such a tool is easy to be applied by general practitioners and cardiologists in order to achieve a fast and objective evaluation of global cardiovascular risk.
Adult↗
[Diabetes in Italy: a public health problem].
BACKGROUND: Type 2 diabetes is the most frequent form of diabetes in the adult population and is associated with an increasing risk of cardiovascular diseases. The objective of this study was to describe the prevalence and the state of control in an Italian population sample examined within the Osservatorio Epidemiologico Cardiovascolare study. METHODS: The sample of this study consisted in 8972 subjects, men and women aged 35-74 years. A fasting capillary blood glucose > or = 126 mg/dl or being on antidiabetic treatment were the criteria used to define diabetes, while a fasting capillary blood glucose < 140 mg/dl was considered to represent effective treatment (controlled diabetes) in treated patients. RESULTS: Diabetes was present in 8.4% of men and 6% in women. The prevalence of glucose intolerance was 8.2% in men and 4.3% in women. Only 50.7% of diabetic men and 56.5% of diabetic women knew about their disease; among these people, 21% was on treatment with oral antidiabetics and/or insulin. Such a therapy was effective in 39.5% of the treated cases. CONCLUSIONS: The prevalence of diabetes as well as glucose intolerance was greater in men and in the regions of the Center and South of Italy. The state of control of diabetes cannot be considered satisfactory; women and older age groups, when prevention strategies are less important, appear to be under better care.
Administration, Oral↗
[Cardiovascular epidemiology: trends of risk factors in Italy].
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Adult↗
[Risk of major first cardiovascular event among men].
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Adult↗
[Risk of major first cardiovascular event among Italian women: results of the CUORE Project].
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Adult↗
[Evaluation of the global cardiovascular absolute risk: the Progetto CUORE individual score].
To identify individuals at high risk for cardiovascular disease, the function of the Progetto CUORE has been identified and the global cardiovascular risk score has been built using data from different cohorts enrolled in the North, Center and South of Italy between the 80s and the 90s, whose risk factors had been collected using standardised procedures. A follow-up with a median duration of 9.5 years for men and 8.0 years for women has been achieved. Age, systolic blood pressure, total cholesterol, HDL-cholesterol, smoking habit, diabetes and hypertension treatment have been included in the function; the first major coronary or cerebrovascular event was considered as endpoint; 10-year survival has been assessed both for men and women. Out of 20 647 people aged 35-69 years with no previous cardiovascular events, 971 major cardiovascular events (636 coronary and 335 cerebrovascular) have been identified and validated. Risk factors coefficients have been assessed using the Cox proportional hazard model separately for men and women. The individual score is easy to be applied by general practitioners and cardiologists in order to achieve a fast and objective evaluation of the absolute global cardiovascular risk in primary prevention.
Adult↗
Recombinant expression of the Ca(2+)-sensitive aspartate/glutamate carrier increases mitochondrial ATP production in agonist-stimulated Chinese hamster ovary cells.
The Ca(2+)-sensitive dehydrogenases of the mitochondrial matrix are, so far, the only known effectors to allow Ca2+ signals to couple the activation of plasma membrane receptors to the stimulation of aerobic metabolism. In this study, we demonstrate a novel mechanism, based on Ca(2+)-sensitive metabolite carriers of the inner membrane. We expressed in Chinese hamster ovary cells aralar1 and citrin, aspartate/glutamate exchangers that have Ca(2+)-binding sites in their sequence, and measured mitochondrial Ca2+ and ATP levels as well as cytosolic Ca2+ concentration with targeted recombinant probes. The increase in mitochondrial ATP levels caused by cell stimulation with Ca(2+)-mobilizing agonists was markedly larger in cells expressing aralar and citrin (but not truncated mutants lacking the Ca(2+)-binding site) than in control cells. Conversely, the cytosolic and the mitochondrial Ca2+ signals were the same in control cells and cells expressing the different aralar1 and citrin variants, thus ruling out an indirect effect through the Ca(2+)-sensitive dehydrogenases. Together, these data show that the decoding of Ca2+ signals in mitochondria depends on the coordinate activity of mitochondrial enzymes and carriers, which may thus represent useful pharmacological targets in this process of major pathophysiological interest.
Adenosine Triphosphate↗
The mitochondrial oxoglutarate carrier: structural and dynamic properties of transmembrane segment IV studied by site-directed spin labeling.
The structural and dynamic features of the fourth transmembrane segment of the mitochondrial oxoglutarate carrier were investigated using site-directed spin labeling and electron paramagnetic resonance (EPR). Using a functional carrier protein with native cysteines replaced with serines, the 18 consecutive residues from S184 to S201 which are believed to form the transmembrane segment IV were substituted individually with cysteine and labeled with a thiol-selective nitroxide reagent. Most of the labeled mutants exhibited significant oxoglutarate transport in reconstituted liposomes, where they were examined by EPR as a function of the incident microwave power in the presence and absence of two paramagnetic perturbants, i.e., the hydrophobic molecular oxygen or the hydrophilic chromium oxalate complex. The periodicity of the sequence-specific variation in the spin-label mobility and the O(2) accessibility parameters unambiguously identifies the fourth transmembrane segment of the mitochondrial oxoglutarate carrier as an alpha-helix. The accessibility to chromium oxalate is out of phase with oxygen accessibility, indicating that the helix is amphipatic, with the hydrophilic face containing the residues found to be important for transport activity by site-directed mutagenesis and chemical modification. The helix is strongly packed, as indicated by the values of normalized mobility, which also suggest that the conformational changes occurring during transport probably involve the N-terminal region of the helix.
Animals↗
Identification of a mitochondrial transporter for basic amino acids in Arabidopsis thaliana by functional reconstitution into liposomes and complementation in yeast.
We describe the identification and functional characterization of two Arabidopsis mitochondrial basic amino acid carriers (BAC), AtmBAC1 and AtmBAC2, which are related to the yeast ornithine (Orn) carrier Ort1p, also known as Arg11p. The arg11 mutant requires arginine (Arg) supplementation because it fails to export sufficient ornithine from the mitochondrion to the cytosol where it is converted to arginine. AtmBAC1 and, to a lesser extent, AtmBAC2 partially replaced the function of Ort1p in yeast arg11. The more efficient putative carrier, AtmBAC1, was expressed in E. coli, purified, and reconstituted into phospholipid vesicles, where it transported the basic l-amino acids arginine, lysine, ornithine and histidine (in order of decreasing affinity). AtmBAC1 recognized l-histidine whereas both yeast Ort1p and the mammalian ortholog ORNT1p do not. Also different from ORNT1p, AtmBAC1 did not transport citrulline. AtmBAC1 appeared to be more stereospecific than the yeast and mammalian ornithine carriers, exhibiting greater preference for the l-forms of arginine, lysine and ornithine. By RT-PCR, both AtmBAC1 and AtmBAC2 transcripts were detected in stems, leaves, flowers, siliques, and seedlings. Expression of AtmBAC1 in seedlings is consistent with its involvement in Arg breakdown in early seedling development, i.e. delivery of Arg to mitochondrial arginase. The Km (0.19 mm) for Arg uptake by AtmBAC1 was close to the value we previously determined for the saturable component of Arg uptake into intact mitochondria from soybean seedling cotyledons.
Amino Acid Sequence↗
The peroxisomal transporter gene ANT1 is regulated by a deviant oleate response element (ORE): characterization of the signal for fatty acid induction.
Saccharomyces cerevisiae ANT1/YPR128c encodes the peroxisomal adenine nucleotide transporter that provides ATP for intra-peroxisomal activation of medium-chain fatty acids. A lacZ reporter construct comprising the ANT1 promoter was shown to be comparatively more highly expressed in a wild-type strain grown on oleic acid, a long-chain fatty acid, than in pip2Delta(oaf1)Delta mutant cells that are defective in fatty acid induction. The ANT1 promoter was demonstrated to contain a deviant oleate response element (ORE) that could bind the Pip2p-Oaf1p transcription factor and confer activation on a basal CYC1-lacZ reporter gene. Expression of Ant1p as well as other enzymes whose genes are known to be regulated by a canonical ORE was found to be increased in cells grown on lauric acid, a medium-chain fatty acid. We concluded that the signal for induction does not differentiate between long- and medium-chain fatty acids. This signal was independent of beta-oxidation or the biogenesis of the peroxisomal compartment where this process occurs, since a pox1Delta strain blocked in the first and rate-limiting step of beta-oxidation as well as various pex mutant cells devoid of intact peroxisomes produced sufficient amounts of Pip2p-Oaf1p for binding OREs in vitro and for expressing an ORE-driven reporter gene. The signal's durability was shown to be related to the concentration of fatty acids in the medium, since a pex6Delta strain expressed an ORE-driven reporter gene at high levels for a longer period than did isogenic wild-type cells. Generation of the signal was also independent of protein synthesis, as demonstrated by cycloheximide treatment.
Adenosine Triphosphate↗
Identification of a novel transporter for dicarboxylates and tricarboxylates in plant mitochondria. Bacterial expression, reconstitution, functional characterization, and tissue distribution.
A cDNA from Arabidopsis thaliana and four related cDNAs from Nicotiana tabacum that we have isolated encode hitherto unidentified members of the mitochondrial carrier family. These proteins have been overexpressed in bacteria and reconstituted into phospholipid vesicles. Their transport properties demonstrate that they are orthologs/isoforms of a novel mitochondrial carrier capable of transporting both dicarboxylates (such as malate, oxaloacetate, oxoglutarate, and maleate) and tricarboxylates (such as citrate, isocitrate, cis-aconitate, and trans-aconitate). The newly identified dicarboxylate-tricarboxylate carrier accepts only the single protonated form of citrate (H-citrate2-) and the unprotonated form of malate (malate2-) and catalyzes obligatory, electroneutral exchanges. Oxoglutarate, citrate, and malate are mutually competitive inhibitors, showing K(i) close to the respective K(m). The carrier is expressed in all plant tissues examined and is largely spread in the plant kingdom. Furthermore, nitrate supply to nitrogen-starved tobacco plants leads to an increase in its mRNA in roots and leaves. The dicarboxylate-tricarboxylate carrier may play a role in important plant metabolic functions requiring organic acid flux to or from the mitochondria, such as nitrogen assimilation, export of reducing equivalents from the mitochondria, and fatty acid elongation.
Arabidopsis↗
Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms.
The mitochondrial carriers are a family of transport proteins in the inner membranes of mitochondria. They shuttle substrates, metabolites, and cofactors through this membrane and connect cytoplasm functions with others in the matrix. Glutamate is co-transported with H(+) (or exchanged for OH(-)), but no protein has ever been associated with this activity. Two human expressed sequence tags encode proteins of 323 and 315 amino acids with 63% identity that are related to the aspartate-glutamate carrier, a member of the carrier family. They have been overexpressed in Escherichia coli and reconstituted into phospholipid vesicles. Their transport properties demonstrate that the two proteins are isoforms of the glutamate/H(+) symporter described in the past in whole mitochondria. Isoform 1 is expressed at higher levels than isoform 2 in all the tissues except in brain, where the two isoforms are expressed at comparable levels. The differences in expression levels and kinetic parameters of the two isoforms suggest that isoform 2 matches the basic requirement of all tissues especially with respect to amino acid degradation, and isoform 1 becomes operative to accommodate higher demands associated with specific metabolic functions such as ureogenesis.
Amino Acid Transport System X-AG↗
Adenine nucleotide translocator 1 deficiency associated with Sengers syndrome.
Sengers syndrome is characterized by congenital cataracts, hypertrophic cardiomyopathy, mitochondrial myopathy, and lactic acidosis, but no abnormalities have been found with routine mitochondrial biochemical diagnostics (the determination of pyruvate oxidation rates and enzyme measurements). In immunoblot analysis, the protein content of the mitochondrial adenine nucleotide translocator 1 (ANT1) was found to be strongly reduced in the muscle tissues of two unrelated patients with Sengers syndrome. In addition, low residual adenine nucleotide translocator activity was detected upon the reconstitution of detergent-solubilized mitochondrial extracts from the patients' skeletal or heart muscle into liposomes. Sequence analysis and linkage analysis showed that ANT1 was not the primary genetic cause of Sengers syndrome. We propose that transcriptional, translational, or posttranslational events are responsible for the ANT1 deficiency associated with the syndrome.
Biological Transport↗
Anxiety, depression and informed consent in patients referred to a radiotherapy department.
AIMS AND BACKGROUND: Informing cancer patients is an ethical, legal and deontological aspect of patient management. Patients need clear instructions in order to be able to accept or refuse medical procedures. Many reports in the literature have shown differences among physicians in informing cancer patients. The aim of this study was to assess patients' understanding of diagnosis, planned radiotherapy and risk of early and late effects, their satisfaction with the discussion with the doctor and correlation with anxiety and depression after the disclosure of a cancer diagnosis. METHODS: From April to July 2000 a physician with psychiatric training conducted interviews with patients after their consultation with the radiotherapist and asked them to fill in a questionnaire. Anxiety and depression were measured by means of a scoring system [HAD(A) and HAD(D)] such as the patient's satisfaction and the physician's belief in it. Eighty-two outpatients referred to our radiotherapy department were studied. RESULTS: We did not find any correlation between HAD(A) and HAD(D) scores and comprehension scores of disease, treatment schedule, side effects and patient satisfaction, or between any scores and presumed predictive variables such as diagnosis, gender, age, treatment aims, time from diagnosis, education, marital status, profession, life habits, and the role of the doctor obtaining the informed consent. CONCLUSIONS: We may conclude that informed consent does not seem to increase reactive anxiety or depression. Its quality is high in our department but must be improved.
Adult↗