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Hisashi Kato, Shinya Masuda, Tomotaka Ohira, Luna Ohira, Hisashi Takakura, Yoshinobu Ohira, Tetsuya Izawa
β-Guanidinopropionic acid (β-GPA) feeding inhibits growth-associated gain of body mass. It remains unknown, however, whether and how β-GPA feeding affects growth-associated increase in white adipose tissue (WAT) mass. We examined the effects of 4- and 8-week β-GPA feeding on serum myostatin levels and expression of genes and proteins related to adipogenesis, lipolysis, and liposynthesis in epididymal WAT (eWAT) and brown adipose tissue (BAT) in 3-week-old, juvenile male mice. Body, eWAT, and muscle weights were significantly lower in β-GPA-fed mice than in controls after feeding...
March 2018: Physiological Reports
Dalon P White, Bradley L Baumgarner, Wade O Watanabe, Md Shah Alam, Stephen T Kinsey
β-guanidinopropionic acid (β-GPA) has been used in mammalian models to reduce intracellular phosphocreatine (PCr) concentration, which in turn lowers the energetic state of cells. This leads to changes in signaling pathways that attempt to re-establish energetic homeostasis. Changes in those pathways elicit effects similar to those of exercise such as changes in body and muscle growth, metabolism, endurance and health. Generally, exercise effects are beneficial to fish health and aquaculture, but inducing exercise in fishes can be impractical...
February 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Fares A Karamat, Deborah L Horjus, Yentl C Haan, Lisa van der Woude, Marianne C Schaap, Inge Oudman, Gert A van Montfrans, Rienk Nieuwland, Gajja S Salomons, Joseph F Clark, Lizzy M Brewster
AIMS: Increasing evidence indicates that the ATP-generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, it has been shown that beta-guanidinopropionic acid (GPA), a kidney-synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. To further develop the substance as a potential blood pressure-lowering agent, we assessed the tolerability of a sub-therapeutic GPA dose in healthy men...
December 2017: British Journal of Clinical Pharmacology
Trenton T Ross, Jeffrey D Overton, Katelyn F Houmard, Stephen T Kinsey
Treatments that increase basal metabolic rate (BMR) and enhance exercise capacity may be useful therapeutic approaches for treating conditions such as type 2 diabetes, obesity, and associated circulatory problems. β -guanidinopropionic acid ( β -GPA) supplementation decreases high-energy phosphate concentrations, such as ATP and phosphocreatine (PCr) resulting in an energetic challenge that is similar to both exercise programs and hypoxic conditions. In this study, we administered β -GPA to mice for 2 or 6 weeks, and investigated the effect on muscle energetic status, body and muscle mass, muscle capillarity, BMR, and normoxic and hypoxic exercise tolerance (NET and HET, respectively)...
March 2017: Physiological Reports
Fares A Karamat, Inge Oudman, Yentl C Haan, Andre B P van Kuilenburg, Rene Leen, Jan A H Danser, Frank P J Leijten, Carrie Ris-Stalpers, Gert A van Montfrans, Joseph F Clark, Lizzy M Brewster
OBJECTIVE: Creatine kinase is reported to be a main predictor of blood pressure (BP) in the general population, with a strong correlation between resistance artery creatine kinase expression and clinical BP in humans. The enzyme rapidly regenerates ATP near cytoplasmic ATPases involved in pressor responses, including resistance artery contractility and renal sodium retention. Therefore, we assessed whether creatine kinase inhibition reduces BP. METHODS: We implemented the 'Animal Research: Reporting of In Vivo Experiments' guideline...
December 2016: Journal of Hypertension
F A Karamat, D Horjus, Y Haan, L Van Der Woude, M Schaap, I Oudman, G Van Montfrans, R Nieuwland, J Clark, A Sturk, L Brewster
OBJECTIVE: There is increasing evidence that the ATP generating enzyme creatine kinase (CK) is involved in hypertension. The enzyme is central to the regeneration of ATP by using creatine phosphate and ADP, thereby forming creatine and ATP. We recently showed that beta-guanidinopropionic acid (GPA), a creatine analogue and competitive CK inhibitor, effectively and safely reduced blood pressure in the spontaneously hypertensive rat. This renders GPA to be potentially beneficial for blood pressure lowering...
September 2016: Journal of Hypertension
Rizwan Ali Zounr, Mumammad Yar Khuhawar, Taj Muhammad Jahangir, Malik Alamgir
An improved GC method in terms of sensitivity and decrease in the analysis time has been developed for the analysis of eight guanidino compounds: guanidine (G), methylguanidine (MG), creatinine (CTN), guanidinoacetic acid (GAA), guanidinobutyric acid (GBA), guanidinopropionic acid (GPA), argenine (Arg), and guanidinosuccinic acid (GSA), using isovaleroylacetone (IVA) and ethyl chloroformate (ECF) as derivatizing reagents. The separation was obtained from column HP-5 (30 m × 0.32 mm i.d.) with film thickness of 0...
2016: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
Si Yang, Li-Hong Long, Di Li, Jian-Kang Zhang, Shan Jin, Fang Wang, Jian-Guo Chen
Previous studies have demonstrated that AMP-activated protein kinase (AMPK) controls autophagy through the mammalian target of rapamycin (mTOR) and Unc-51 like kinase 1 (ULK1/Atg1) signaling, which augments the quality of cellular housekeeping, and that β-guanidinopropionic acid (β-GPA), a creatine analog, leads to a chronic activation of AMPK. However, the relationship between β-GPA and aging remains elusive. In this study, we hypothesized that feeding β-GPA to adult Drosophila produces the lifespan extension via activation of AMPK-dependent autophagy...
December 2015: Aging Cell
Fares A Karamat, Deborah L Horjus, Yentl C Haan, Lisa van der Woude, Inge Oudman, Gert A van Montfrans, Joseph F Clark, Lizzy M Brewster
BACKGROUND: Despite adequate treatment, up to 30% of treated antihypertensive patients with primary, uncomplicated hypertension remain uncontrolled. We proposed that high intracellular activity of the ATP regenerating enzyme creatine kinase (CK) increases pressor responses and hypertension risk. In line with this, we found that plasma CK activity after rest, a surrogate measure of tissue activity, is the main predictor of blood pressure levels and failure of antihypertensive therapy in the general population...
February 22, 2015: Trials
Bradley L Baumgarner, Alison M Nagle, Meagan R Quinn, A Elaine Farmer, Stephen T Kinsey
Increased AMP-activated protein kinase (AMPK) activity leads to enhanced fatty acid utilization, while also promoting increased ubiquitin-dependent proteolysis (UDP) in mammalian skeletal muscle. β-guanidinopropionic acid (βGPA) is a commercially available dietary supplement that has been shown to promote an AMPK-dependent increase in fatty acid utilization and aerobic capacity in mammals by compromising creatine kinase function. However, it remains unknown if continuous βGPA supplementation can negatively impact skeletal muscle growth in a rapidly growing juvenile...
May 2015: Molecular and Cellular Biochemistry
Tracy L Scheffler, Steven C Kasten, Eric M England, Jason M Scheffler, David E Gerrard
Pigs with the AMP-activated protein kinase γ3 R200Q (AMPKγ3(R200Q)) mutation generate pork with low ultimate pH (pHu). We hypothesized that reducing muscle creatine (Cr) and phosphocreatine (PCr) may accelerate postmortem ATP consumption and prevent extended pH decline in AMPKγ3(R200Q) longissimus muscle. Wild type and AMPKγ3(R200Q) pigs were assigned to control diet or diet supplemented with the creatine analog β-guanidinopropionic acid (β-GPA, 1%) for 2 wk. β-GPA reduced muscle PCr (P = 0.006) and total Cr (P<0...
February 2014: Meat Science
Laetitia Van Noolen, Denis Monneret, Véronique Ducros, Christelle Corne, Joël Lunardi, Patrice Faure
Guanidinoacetate (GAA) and creatine (Cr) are creatine deficiency syndromes (CDS) biochemical markers. We describe a liquid chromatography - tandem mass spectrometry method (LC/MSMS) performing simultaneous analysis of GAA, Cr and creatinine (Crn). Study of Cr uptake by fibroblasts for Cr transporter defect diagnosis is also assessed. The three butylated compounds were separated by liquid chromatography and MSMS quantification was achieved by isotopic dilution with electrospray positive ion mode. Linearity was demonstrated from 0 to 600, 675 and 4500 μmol/L and limit of quantification was 0...
July 2013: Annales de Biologie Clinique
Takuya Usui, Yoshiyuki Kubo, Shin-Ichi Akanuma, Ken-Ichi Hosoya
The supply of L-carnosine, a bioactive dipeptide of β-alanine and l-histidine, to the retina across the blood-retinal barrier (BRB) was studied. The in vivo and in vitro studies revealed low uptake activities for [(3)H]Gly-Sar, a representative dipeptide, suggesting that l-carnosine transport plays only a minor role at the BRB. The in vivo study using rats showed approximately 18- and 23-fold greater retinal uptake indexes (RUI) for [(3)H]β-alanine and [(3)H]l-histidine compared with that of a paracellular marker, respectively...
August 2013: Experimental Eye Research
T L Scheffler, A L Rosser, S C Kasten, J M Scheffler, D E Gerrard
Rate and extent of postmortem metabolism control pork quality development. Our objective was to evaluate the role of the phosphagen system (phosphocreatine, PCr; and creatine, Cr) on metabolism and pork quality. Muscle PCr and Cr were manipulated by feeding pigs the creatine analogue, β-guanidinopropionic acid (β-GPA). In experiment 1, pigs received standard (control) diet or β-GPA supplemented (2%) diet (1 wk or 2 wk). Supplementation with β-GPA (2 wk) decreased total Cr (PCr+Cr; P=0.02) and improved pork color (decreased reflectance, P=0...
October 2013: Meat Science
Allen Herbst, Chad J Johnson, Kayla Hynes, Debbie McKenzie, Judd M Aiken
Aged muscles possess dysfunctional fibers that contain intracellular expansions of somatically derived mitochondrial DNA deletion mutations. At high abundance, these mutations disrupt the expression of mitochondrially-encoded protein subunits of the electron transport chain resulting in aerobic respiration deficient muscle fiber segments. These fiber segments atrophy and break contributing to the loss of muscle mass and function that occurs with age. By combining micro-dissection of individual muscle fibers with microarray analysis, we observed the response induced within these abnormal muscle fibers and detected an increase in many genes affecting metabolism and metabolic regulation...
2013: PloS One
Yusuke Maeda, Rintaro Iwata, Takeshi Wada
A series of artificial peptides bearing cationic functional groups with different side chain lengths were designed, and their ability to increase the thermal stability of nucleic acid duplexes was investigated. The peptides with amino groups selectively increased the stability of RNA/RNA duplexes, and a relationship between the side chain length and the melting temperature (Tm) of the peptide-RNA complexes was observed. On the other hand, while peptides with guanidino groups exhibited a similar tendency with respect to the peptide structure and thermal stability of RNA/RNA duplexes, those with longer side chain lengths, such as L-2-amino-4-guanidinobutyric acid (Agb) or L-arginine (Arg) oligomers, stabilized both RNA/RNA and DNA/DNA duplexes, and those with shorter side chain lengths exhibited a higher ability to selectively stabilize RNA/RNA duplexes...
April 1, 2013: Bioorganic & Medicinal Chemistry
Subhan Ali Majidano, Muhammad Yar Khuhawar
Gas chromatographic (GC) method has been developed for the determination of the guanidino compounds: guanidine (G), methylguanidine (MG), guanidinoacetic acid (GAA), guanidinopropionic acid (GPA), guanidinobutyric acid (GBA) and guanidinosuccinic acid (GSA) was carried out after precolumn derivatization with glyoxal and ethyl chloroformate from the column HP-5 (30 m × 0.32 mm i.d.) at 90°C for 3 min, followed by a heating rate 25°C/min up to 260°C with a nitrogen flow rate of 2 ml/min. Detection was by FID...
2013: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
Inge Oudman, Joseph F Clark, Lizzy M Brewster
BACKGROUND: Creatine kinase plays a key role in cellular energy transport. The enzyme transfers high-energy phosphoryl groups from mitochondria to subcellular sites of ATP hydrolysis, where it buffers ADP concentration by catalyzing the reversible transfer of the high-energy phosphate moiety (P) between creatine and ADP. Cellular creatine uptake is competitively inhibited by beta-guanidinopropionic acid. This substance is marked as safe for human use, but the effects are unclear. Therefore, we systematically reviewed the effect of beta-guanidinopropionic acid on energy metabolism and function of tissues with high energy demands...
2013: PloS One
Edward L D'Antonio, David W Christianson
Human arginase I (HAI) is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of L-arginine to form L-ornithine and urea through a metal-activated hydroxide mechanism. Since HAI regulates L-Arg bioavailability for NO biosynthesis, it is a potential drug target for the treatment of cardiovascular diseases such as atherosclerosis. X-ray crystal structures are now reported of the complexes of Mn(2)(2+)-HAI and Co(2)(2+)-HAI with L-2-amino-3-guanidinopropionic acid (AGPA; also known as dinor-L-arginine), an amino acid bearing a guanidinium side chain two methylene groups shorter than that of L-arginine...
August 1, 2012: Acta Crystallographica. Section F, Structural Biology and Crystallization Communications
Vassili Valayannopoulos, Naziha Bakouh, Michel Mazzuca, Luc Nonnenmacher, Laurence Hubert, Fatna-Léa Makaci, Allel Chabli, Gajja S Salomons, Caroline Mellot-Draznieks, Emilie Brulé, Pascale de Lonlay, Hervé Toulhoat, Arnold Munnich, Gabrielle Planelles, Yves de Keyzer
Intellectual disability coupled with epilepsy are clinical hallmarks of the creatine (Cr) transporter deficiency syndrome resulting from mutations in the SLC6A8 gene. So far characterization of pathogenic mutations of SLC6A8 has been limited to Cr uptake. The aim of our study was to characterize the electrogenic and pharmacological properties of non truncating SLC6A8 mutations identified in patients presenting variable clinical severity. Electrophysiological and pharmacological properties of four mutants (including two novel ones) were studied in X...
January 2013: Journal of Inherited Metabolic Disease
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