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Betaine AND Mitochondria

Mohammad Javad Khodayar, Heibatollah Kalantari, Layasadat Khorsandi, Mohammad Rashno, Leila Zeidooni
Overdose of acetaminophen (APAP) is a common cause of acute liver failure. Oxidative stress and mitochondrial dysfunction are related to APAP-induced hepatotoxicity. This study investigated the protective role of betaine as a methyl donor and S-adenosylmethionine precursor against APAP hepatotoxicity in isolated mice liver mitochondria. We treated male NMRC mice with 125, 250, 500, and 1000 mg/kg betaine for 5 days followed by 300 mg/kg APAP 1 h later. At 24 h after APAP administration, animals were sacrificed and liver mitochondria were isolated by different centrifugation methods...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Eugene P Sokolov, Inna M Sokolova
Salinity is an important environmental factor affecting physiology of marine organisms. Osmoconformers such as marine mollusks maintain metabolic function despite changes of the osmolarity and composition of the cytosol during salinity shifts. Currently, metabolic responses to the salinity-induced changes of the intracellular milieu are not well understood. We studied the effects of osmolarity (450 vs. 900 mOsm) and compatible osmolytes (70-590 mM of taurine or betaine) on isolated gill mitochondria of a marine osmoconformer, the Pacific oyster Crassostrea gigas...
February 16, 2018: Mitochondrion
Huifang Kang, Zhiwang Zhang, Lin Yu, Yixing Li, Mingzhen Liang, Lei Zhou
Fat mass and obesity-associated protein (FTO) is a RNA demethylase, whether FTO regulates fat metabolism through its demethylation is unclear. The results of this study confirmed that N6-methyladenosine (m6 A) is associated with fat accumulation both in vivo and in vitro. The data showed that FTO down-regulated m6 A levels, decreased mitochondrial content, and increased triglyceride (TG) deposition. However, an FTO (R316A) mutant lacking demethylation activity could not regulate mitochondria and TG content, indicating that FTO affects mitochondrial content and fat metabolism by modulating m6 A levels in hepatocytes...
January 31, 2018: Journal of Cellular Biochemistry
Ryohta Nishiyama, Fumiaki Nagashima, Beniko Iwao, Yuiko Kawai, Kana Inoue, Arisa Midori, Tsuyoshi Yamanaka, Hiroyuki Uchino, Masato Inazu
We examined the functional characteristics of choline uptake in human tongue carcinoma using the cell line HSC-3. Furthermore, we explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. Both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were expressed, and were located in plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is pH-dependent. Several cationic drugs inhibited cell viability and [(3)H]choline uptake...
June 2016: Journal of Pharmacological Sciences
Peter F Surai
Silymarin (SM), an extract from the Silybum marianum (milk thistle) plant containing various flavonolignans (with silybin being the major one), has received a tremendous amount of attention over the last decade as a herbal remedy for liver treatment. In many cases, the antioxidant properties of SM are considered to be responsible for its protective actions. Possible antioxidant mechanisms of SM are evaluated in this review. (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut...
March 20, 2015: Antioxidants (Basel, Switzerland)
Naveen Kumar Singhal, Shuo Li, Erland Arning, Kholoud Alkhayer, Robert Clements, Zachary Sarcyk, Rohan S Dassanayake, Nicola E Brasch, Ernest J Freeman, Teodoro Bottiglieri, Jennifer McDonough
UNLABELLED: Mitochondrial changes, including decreased expression of electron transport chain subunit genes and impaired energetic, have been reported in multiple sclerosis (MS), but the mechanisms involved in these changes are not clear. To determine whether epigenetic mechanisms are involved, we measured the concentrations of methionine metabolites by liquid chromatography tandem mass spectrometry, histone H3 methylation patterns, and markers of mitochondrial respiration in gray matter from postmortem MS and control cortical samples...
November 11, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Icksoo Lee
Betaine protects cells from environmental stress and serves as a methyl donor in several biochemical pathways. It reduces cardiovascular disease risk and protects liver cells from alcoholic liver damage and nonalcoholic steatohepatitis. Its pretreatment can rescue cells exposed to toxins such as rotenone, chloroform, and LiCl. Furthermore, it has been suggested that betaine can suppress cancer cell growth in vivo and in vitro. Mitochondrial electron transport chain (ETC) complexes generate the mitochondrial membrane potential, which is essential to produce cellular energy, ATP...
January 9, 2015: Biochemical and Biophysical Research Communications
Sungwoo Park, Seon-Guk Choi, Seung-Min Yoo, Jin H Son, Yong-Keun Jung
CHDH (choline dehydrogenase) is an enzyme catalyzing the dehydrogenation of choline to betaine aldehyde in mitochondria. Apart from this well-known activity, we report here a pivotal role of CHDH in mitophagy. Knockdown of CHDH expression impairs CCCP-induced mitophagy and PARK2/parkin-mediated clearance of mitochondria in mammalian cells, including HeLa cells and SN4741 dopaminergic neuronal cells. Conversely, overexpression of CHDH accelerates PARK2-mediated mitophagy. CHDH is found on both the outer and inner membranes of mitochondria in resting cells...
2014: Autophagy
Laila C Schenkel, Ratnesh K Singh, Vera Michel, Steven H Zeisel, Kerry-Ann da Costa, Amy R Johnson, Harvey S Mudd, Marica Bakovic
Fibroblasts from a patient with postural orthostatic tachycardia syndrome (POTS), who presented with low plasma choline and betaine, were studied to determine the metabolic characteristics of the choline deficiency. Choline is required for the synthesis of the phospholipid phosphatidylcholine (PC) and for betaine, an important osmoregulator. Here, choline transport, lipid homeostasis, and mitochondria function were analyzed in skin fibroblasts from POTS and compared with control cells. The choline transporter-like protein 1/solute carrier 44A1 (CTL1/SLC44A1) and mRNA expression were 2-3 times lower in POTS fibroblasts, and choline uptake was reduced 60% (P < 0...
May 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sungwoo Park, Seon-Guk Choi, Seung-Min Yoo, Jin H Son, Yong-Keun Jung
CHDH (choline dehydrogenase) is an enzyme catalyzing the dehydrogenation of choline to betaine aldehyde in mitochondria. Apart from this well-known activity, we report here a pivotal role of CHDH in mitophagy. Knockdown of CHDH expression impairs CCCP-induced mitophagy and PARK2/parkin-mediated clearance of mitochondria in mammalian cells, including HeLa cells and SN4741 dopaminergic neuronal cells. Conversely, overexpression of CHDH accelerates PARK2-mediated mitophagy. CHDH is found on both the outer and inner membranes of mitochondria in resting cells...
August 18, 2014: Autophagy
Y B Wang, L L Guan, Y W Xu, H Shen, W Wu
In response to salinity or drought stress, many plants accumulate glycine betaine, which is a regulator of osmosis. In plants, the last step in betaine synthesis is catalyzed by betaine aldehyde dehydrogenase (BADH), a nuclear-encoded chloroplastic enzyme. Based on the conserved oligo amino acid residues of the published BADH genes from other higher plant species, a cDNA sequence, designated CtBADH, was isolated from safflower (Carthamus tinctorius L.) using a polymerase chain reaction approach. The clones were 1...
2014: Genetics and Molecular Research: GMR
Francesca Salvi, Giovanni Gadda
Human choline dehydrogenase (CHD) is located in the inner membrane of mitochondria primarily in liver and kidney and catalyzes the oxidation of choline to glycine betaine. Its physiological role is to regulate the concentrations of choline and glycine betaine in the blood and cells. Choline is important for regulation of gene expression, the biosynthesis of lipoproteins and membrane phospholipids and for the biosynthesis of the neurotransmitter acetylcholine; glycine betaine plays important roles as a primary intracellular osmoprotectant and as methyl donor for the biosynthesis of methionine from homocysteine, a required step for the synthesis of the ubiquitous methyl donor S-adenosyl methionine...
September 15, 2013: Archives of Biochemistry and Biophysics
Jamie A Meadows, Matthew J Wargo
To survive in various environments, from host tissue to soil, opportunistic bacterial pathogens must be metabolically flexible and able to use a variety of nutrient sources. We are interested in Pseudomonas aeruginosa's catabolism of quaternary amine compounds that are prevalent in association with eukaryotes. Carnitine and acylcarnitines are abundant in animal tissues, particularly skeletal muscle, and are used to shuttle fatty acids in and out of the mitochondria, where they undergo β-oxidation. We previously identified the genes required for carnitine catabolism as the first four genes in the carnitine operon (caiX-cdhCAB; PA5388 to PA5385)...
June 2013: Applied and Environmental Microbiology
Metin Basaranoglu, Gökcen Basaranoglu, Hakan Sentürk
Although much is known about how fat accumulates in the liver, much remains unknown about how this causes sustained hepatocellular injury. The consequences of injury are recognized as nonalcoholic steatohepatitis (NASH) and progressive fibrosis. The accumulation of fat within the hepatocytes sensitizes the liver to injury from a variety of causes and the regenerative capacity of a fatty liver is impaired. An additional stressor is sometimes referred to as a "second hit" in a paradigm that identifies the accumulation of fat as the "first hit"...
February 28, 2013: World Journal of Gastroenterology: WJG
Qian Garrett, Neeta Khandekar, Sharon Shih, Judith L Flanagan, Peter Simmons, Joseph Vehige, Mark D P Willcox
Elevated tear osmolarity is one of the key pathological factors in dry eye leading to ocular discomfort associated with damage to the ocular surface and inflammation. The aim of this study was to determine the capacity of the organic osmolyte, betaine, to act as an osmoprotectant against hypertonic stress-induced human corneal epithelial cell shrinkage and apoptosis using in vitro cell culture models. Human corneal limbal epithelial (HCLE) cells exposed to culture medium for 16 h at 300 mOsm (isotonic) or 500 mOsm (hyperosmotic) in the presence or absence of betaine (5 or 10 mM) were evaluated for cell volume changes; cell viability; and apoptosis...
March 2013: Experimental Eye Research
Steven H Zeisel
There are multiple identified mechanisms involved in energy metabolism, insulin resistance and adiposity, but there are here-to-fore unsuspected metabolic factors that also influence these processes. Studies in animal models suggest important links between choline/1-carbon metabolism and energy homeostasis. Rodents fed choline deficient diets become hypermetabolic. Mice with deletions in one of several different genes of choline metabolism have phenotypes that include increased metabolic rate, decreased body fat/lean mass ratio, increased insulin sensitivity, decreased ATP production by mitochondria, or decreased weight gain on a high fat diet...
March 1, 2013: Clinical Chemistry and Laboratory Medicine: CCLM
Mohammad Reza Eskandari, Javad Khalili Fard, Mir-Jamal Hosseini, Jalal Pourahmad
Lithium preparations are commonly used drug in treating mental disorders and bipolar diseases, but metal's cytotoxic mechanisms have not yet been completely understood. In this study, we investigated the cytotoxic mechanisms of lithium in freshly isolated rat hepatocytes. Lithium cytotoxicity were associated with reactive oxygen species (ROS) formation and collapse of mitochondrial membrane potential and cytochrome c release into the hepatocyte cytosol. All of the mentioned lithium-induced cytotoxicity markers were significantly (P < 0...
October 2012: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Kusum K Kharbanda, Sandra L Todero, Adrienne L King, Natalia A Osna, Benita L McVicker, Dean J Tuma, James L Wisecarver, Shannon M Bailey
Introduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Methods. Male Wister rats were pair-fed control or ethanol-containing liquid diets supplemented with or without betaine (10 mg/mL) for 4-5 wks. Liver was examined for triglyceride accumulation, levels of methionine cycle metabolites, and alterations in mitochondrial proteins...
2012: International Journal of Hepatology
Janis Kuka, Reinis Vilskersts, Helena Cirule, Marina Makrecka, Osvalds Pugovics, Ivars Kalvinsh, Maija Dambrova, Edgars Liepinsh
Mildronate, an inhibitor of L-carnitine biosynthesis and uptake, is a cardioprotective drug whose mechanism of action is thought to rely on the changes in concentration of L-carnitine in heart tissue. In the present study, we compared the cardioprotective effect of mildronate (100 mg/kg) and a combination of mildronate and L-carnitine (100 + 100 mg/kg) administered for 14 days with respect to the observed changes in l-carnitine level and carnitine palmitoyltransferase I (CPT-I)-dependent fatty acid metabolism in the heart tissues...
June 2012: Journal of Cardiovascular Pharmacology and Therapeutics
Emanuela Tassoni, Roberto Conti, Grazia Gallo, Silvia Vincenti, Lucilla Mastrofrancesco, Tiziana Brunetti, Walter Cabri, Fabio Giannessi
No abstract text is available yet for this article.
November 4, 2011: ChemMedChem
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