NAD AND T3

Docosahexaenoic acid (DHA) and 3,3',5-triiodothyronine (T3 ) combined protocol affords protection against liver injury via AMPK signaling supporting energy requirements. The aim of this work was to test the hypothesis that a DHA + T3 accomplish mitochondrial adaptation through downstream upregulation of PPAR-γ coactivator 1α (PGC-1α). Male Sprague-Dawley rats were given daily oral doses of 300 mg DHA/kg or saline (controls) for three consecutive days, followed by 0.05 mg T3 /kg (or hormone vehicle) ip at the fourth day, or single dose of 0...

The thyroid hormone triiodothyronine (T3 ) activates thermogenesis by uncoupling electron transport from ATP synthesis in brown adipose tissue (BAT) mitochondria. Although T3 can induce thermogenesis by sympathetic innervation, little is known about its cell autonomous effects on BAT mitochondria. We thus examined effects of T3 on mitochondrial activity, autophagy, and metabolism in primary brown adipocytes and BAT and found that T3 increased fatty acid oxidation and mitochondrial respiration as well as autophagic flux, mitophagy, and mitochondrial biogenesis...

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides hemodynamic rescue for patients encountering right or left ventricular (RV or LV) decompensation, particularly after surgery for congenital heart defects. ECMO, supported metabolically by parenteral nutrition, provides reductions in myocardial work and energy demand and, therefore, enhances functional recovery. The RV must often assume systemic ventricular pressures and function on weaning from VA-ECMO. However the substrate utilization responses of the RV to VA-ECMO or stimulation are unknown...

Mutations in the gene encoding the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), cause mental retardation in humans associated with a specific thyroid hormone phenotype manifesting high serum T3 and low T4 and rT3 levels. Moreover, these patients have failure to thrive, and physiological changes compatible with thyrotoxicosis. Recent studies in Mct8-deficient (Mct8KO) mice revealed that the high serum T3 causes increased energy expenditure. The TH analog, diiodothyropropionic acid (DITPA), enters cells independently of Mct8 transport and shows thyromimetic action but with a lower metabolic activity than TH...

BACKGROUND: High-level expression of NAD(P)H: quinoneoxidoreductase 1 (NQO1) has been correlated with many types of human cancers, suggesting that NQO1 plays important roles in tumor occurrence and progression. This study attempted to explore the role of NQO1 in tumor progression and prognostic evaluation of non-small cell lung cancer (NSCLC). METHODS: Total 164 tissue samples, including 150 NSCLC paired with the adjacent non-tumor tissues and 14 normal lung tissues, were picked-up for immunohistochemical (IHC) staining of the NQO1 protein, and immunofluorescence (IF) staining was also performed to detect the subcellular localization of the NQO1 protein in A549 human lung cancer cells...

Resveratrol (RSV) is a plant polyphenol that exhibits several favorable effects on glucose homeostasis in adipocytes. Recent studies from our laboratory demonstrated that coplanar polychlorinated biphenyls (PCBs) that are ligands of the aryl hydrocarbon receptor impair glucose homeostasis in mice. PCB-induced impairment of glucose homeostasis was associated with augmented expression of inflammatory cytokines in adipose tissue, a site for accumulation of lipophilic PCBs. This study determined if RSV protects against PCB-77 induced impairment of glucose disposal in vitro and in vivo and if these beneficial effects are associated with enhanced nuclear factor erythoid 2-related factor 2 (Nrf2) signaling in adipose tissue...

Sirtuin 1 (SIRT1) NAD(+)-dependent deacetylase regulates energy metabolism by modulating expression of genes involved in gluconeogenesis and other liver fasting responses. While many effects of SIRT1 on gene expression are mediated by deacetylation and activation of peroxisome proliferator activated receptor coactivator α (PGC-1α), SIRT1 also binds directly to DNA bound transcription factors, including nuclear receptors (NRs), to modulate their activity. Since thyroid hormone receptor β1 (TRβ1) regulates several SIRT1 target genes in liver and interacts with PGC-1α, we hypothesized that SIRT1 may influence TRβ1...

BACKGROUND: Sonchus asper (L.) Hill, (Asteraceae) is used in Pakistan as a traditional ("folk") medicine for the treatment of hormonal disorders and oxidative stress. The present study was aimed to evaluate the efficacy of Sonchus asper (L.) Hill, (Asteraceae) methanolic extract (SAME) on hormonal dysfunction in thyroid tissue after carbon tetrachloride (CCl4)-induced oxidative stress. METHODS: To examine the effects of SAME against the oxidative stress of CCl4 in thyroid tissue, 30 male albino rats were used...

Chemical coding of sympathetic preganglionic neurons (SPN) suggests that the chemical content of subpopulations of SPN can define their function. Since neuropeptides, once synthesized are transported to the axon terminal, most demonstrated chemical coding has been identified using immunoreactive terminals at the target organ. Here, we use a different approach to identify and quantify the subpopulations of SPN that contain the mRNA for pituitary adenylate cyclase activating polypeptide (PACAP) or enkephalin...

BACKGROUND: A phase II trial to evaluate neoadjuvant (NAD), surgery and adjuvant (AD) combination chemotherapy without radiation therapy (RT) for patients with esophageal adenocarcinoma staged with endoscopic ultrasound and CT as T3N1 was carried out. METHODS: Thirty-three eligible patients were enrolled. NAD therapy was administered in two 49-day cycles and included cisplatin, floxuridine, paclitaxel and leucovorin. Esophageal resection was performed followed by AD therapy...

Myocardial and endothelial damage is still a widely debated problem during the ischemia-reperfusion sequence in heart surgery. We evaluated myocardial purine metabolites, antioxidant defense mechanisms, oxidative status and endothelial dysfunction markers in 14 patients undergoing coronary artery by-pass graft (CABG). Heart biopsies were taken before aortic cross-clamping (t1), before clamp removal (t2) and 30 min after reperfusion (t3); perchloric extracts of the tissue were analyzed for glutathione, NAD, nucleotide nucleoside and base content by capillary electrophoresis (CE)...

A cytosolic thyroid-hormone-binding protein (xCTBP), predominantly responsible for the major binding activity of T3 in the cytosol of Xenopus liver, has been shown to be identical to aldehyde dehydrogenase class 1 (ALDH1) [Yamauchi, K., Nakajima, J., Hayashi, H., Horiuchi, R. & Tata, J.R. (1999) J. Biol. Chem. 274, 8460-8469]. Within this paper we surveyed which signaling, and other, compounds affect the thyroid hormone binding activity and aldehyde dehydrogenase activity of recombinant Xenopus ALDH1 (xCTBP/xALDH1) while examining the relationship between these two activities...

This work examined the role of constitutional genetic variation at the glutathione S-transferase M1 (GSTM1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) detoxification loci in breast cancer development. Methods included contrasting patterns of genetic variations at these loci between cases with breast cancer and healthy controls and assessing the association of genotypes with tumor characteristics. Participants were Caucasian women living in the Greater Philadelphia region, recruited from 1988 to 1994, with recently diagnosed women attending breast cancer clinics at Fox Chase Cancer Center (FCCC) and network affiliated hospitals as cases, and FCCC employees or women attending noncancer clinics as controls...

Thyroid hormone can potentially regulate the malate/aspartate and alpha-glycerophosphate shuttle pathways in cardiac mitochondria either directly, by altering gene expression, or indirectly, by increasing myocardial workload. The goal of the current study was to determine the influence of thyroid hormone on the NADH shuttles in cardiac and liver mitochondria. Malate/aspartate and alpha-glycerophosphate shuttle capacities were significantly increased in cardiac mitochondria from adult rats treated for 9 days with T3 compared to saline-treated controls...

Leydig cells were isolated from the perch testes belonging to the pre-spawning stage by collagenase treatment and mechanical separation followed by percoll gradient. They were incubated in vitro either for 5 h or at different times in the absence (control) or presence of piscine gonadotropin (GTH, 2 microg (1 x 10(6) cells)(-1)) or 3,5,3'-triiodothyronine (T3, 50 ng (1 x 10(6) cells(-1)) or T3-induced protein (TIP, 2 microg (1 x 10(6) cells)(-1)). 3Beta-hydroxysteroid dehydrogenase/delta5-delta4-isomerase (3beta-HSD) activity was determined by the conversion of [3H]delta5-dehydroepiandrosterone (DHEA) to [3H]delta4-androstenedione or [3H]delta5-pregnenolone to [3H]delta4-progesterone (P4) or by spectrophotometric estimation of NADH formation from NAD...

Amino acid sequencing of an internal peptide fragment derived from purified Xenopus cytosolic thyroid hormone-binding protein (xCTBP) demonstrates high similarity to the corresponding sequence of mammalian aldehyde dehydrogenase 1 (ALDH1) (Yamauchi, K., and Tata, J. R. (1994) Eur. J. Biochem. 225, 1105-1112). Here we show that xCTBP was co-purified with ALDH and 3,3',5-triiodo-L-thyronine (T3) binding activities. By photoaffinity labeling with [125I]T3, a T3-binding site in the xCTBP was estimated to reside in amino acid residues 93-114, which is distinct from the active site of the enzyme but present in the NAD+ binding domain...

Ovarian follicles were collected from perch belonging to the prespawning (vitellogenic) stage and incubated in vitro for 5 h in the absence (control) and presence of 3, 5, 3'-triiodothyronine (T3). Addition of increasing concentrations of T3 from 12.5 to 100 ng/ml caused a linear increase of 3beta-hydroxysteroid dehydrogenase/delta5-delta4-isomerase (3 beta-HSD) activity to 50 ng and then it leveled off indicating a saturation of enzyme activity with 50 ng T3. T3 stimulation of 3beta-HSD activity could be blocked by cycloheximide indicating the involvement of T3-induced protein (TIP) isolated and purified earlier from this laboratory...

Cyclic ADP-ribose (cADPR) is a nucleotide synthesized from beta-NAD- that can trigger or facilitate Ca2+-release through ryanodine-channels. We investigated the synthesis of cADPR (ADPR-cyclase activity) in cultured vascular smooth muscle cells (VSMC) from rat aorta in response to incubation with all-trans-retinoic acid (RA), 3,3',5'-triiodothyronine (T3), cortisol, beta-estradiol and 1-dehydrotestosterone. Only RA and T3 caused concentration-dependent (10(-9)-10(-6) M) stimulation of ADPR-cyclase activity in VSMC...

Addition of triiodothyronine at 10 pM in vitro to hypothyroid rat liver mitochondria doubles the rate of the adenine nucleotide transporter at low ADP concentrations. Nicotinamide abolishes this effect in parallel with its inhibition of the ADP-ribosylation of an inner membrane protein identical in size to the transporter. Nicotinamide also renders euthyroid preparations indistinguishable from hypothyroid ones. A mechanism is offered to explain these findings in which it is proposed that the adenine nucleotide transporter is a true allosteric protein and that its covalent modification by ADP-ribosylation increases the stability of the less favoured externally-facing C-conformation and thus increases the proportion of transporters in this orientation: although the C-conformation is significantly more leaky to cations than the tight matrix-facing M-conformation, this enhances ADP import...

Eukaryotic initiation factor 5A (eIF-5A) is the only cellular protein known to contain a hypusine residue that is formed by transferring the aminobutyl moiety from spermidine to a specific lysine residue, followed by hydroxylation at the aminobutyl group. A simple PCR-based strategy was developed to obtain a full-length cDNA of Neurospora crassa eIF-5A. The strategy consists of (i) the design of a pair of key primers (21-mer) based on the highly conserved eIF-5A cDNA domains known in other species, (ii) PCR amplification of Neurospora cDNA using the two key primers to obtain the core sequence for the design of core primers, and (iii) combined use of the key primers, core primers and the universal primers, T3 and T7, to amplify the target sequence in a Neurospora cDNA library...