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Suppressed expression of LDHB promotes age-related hearing loss via aerobic glycolysis.
Cell Death Dis
May 2020
Department of Otolaryngology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
Age-dependent decrease of mitochondrial energy production and cellular redox imbalance play significant roles in age-related hearing loss (ARHL). Lactate dehydrogenase B (LDHB) is a key glycolytic enzyme that catalyzes the interconversion of pyruvate and lactate. LDH activity and isoenzyme patterns are known to be changed with aging, but the role of LDHB in ARHL has not been studied yet.
View Article and Find Full Text PDFThe Puzzling Role of Neuron-Specific PMCA Isoforms in the Aging Process.
Int J Mol Sci
December 2019
Department of Molecular Neurochemistry, Medical University, 92-215 Lodz, Poland.
The aging process is a physiological phenomenon associated with progressive changes in metabolism, genes expression, and cellular resistance to stress. In neurons, one of the hallmarks of senescence is a disturbance of calcium homeostasis that may have far-reaching detrimental consequences on neuronal physiology and function. Among several proteins involved in calcium handling, plasma membrane Ca-ATPase (PMCA) is the most sensitive calcium detector controlling calcium homeostasis.
View Article and Find Full Text PDFCoexpression of Human Hepatic Uridine Diphosphate Glucuronosyltransferase Proteins: Implications for Ontogenetic Mechanisms and Isoform Coregulation.
J Clin Pharmacol
June 2020
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Uridine diphosphate glucuronosyltransferases (UGTs) catalyze glucuronidation to facilitate systemic and local clearance of numerous chemicals and drugs. To investigate whether UGT expression is coregulated in human liver, we analyzed the protein expression of UGTs 1A1, 1A3, 1A4, 1A6, 1A9, 2B7, 3A1, and 3A2 using western blots from 164 healthy human liver samples, comparing expression with age and sex. UGT1A6 levels were significantly higher in children than adults, and UGT3A1 and 3A2 expression significantly increased with age from childhood to age >65 yearas.
View Article and Find Full Text PDFToward precision medicine in pediatric population using cytochrome P450 phenotyping approaches and physiologically based pharmacokinetic modeling.
Pediatr Res
February 2020
Department of Acute Medicine, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
The activity of drug-metabolizing enzymes (DME) shows high inter- and intra-individual variability. Genetic polymorphisms, exposure to drugs, and environmental toxins are known to significantly alter DME expression. In addition, the activity of these enzymes is highly age-dependent due to maturation processes that occur during development.
View Article and Find Full Text PDFCharacterization of the Ontogeny of Hepatic UDP-Glucuronosyltransferase Enzymes Based on Glucuronidation Activity Measured in Human Liver Microsomes.
J Clin Pharmacol
September 2019
Pharmaceutical Sciences, Roche Pharma Research and Early Development, Roche Innovation Centre Basel, Basel, Switzerland.
An understanding of the postnatal development of hepatic UDP-glucuronosyltransferase (UGT) enzymes is required for accurate prediction of the age-dependent changes in pharmacokinetics of many drugs used in children. However, the maturation rate of hepatic UGT isoforms remains a major knowledge gap. This study aimed to establish the age-associated changes in glucuronidation activity of 10 major hepatic UGT isoforms in humans, namely, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17.
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