A5067648589- Mitochondrial Function and Pathology
- Alzheimer's disease research and treatments
- Metabolism and Genetic Disorders
- Down syndrome and intellectual disability research
- Retinal Diseases and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Retinal Imaging and Analysis
- Nigella sativa pharmacological applications
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- Corneal surgery and disorders
- Genetic Syndromes and Imprinting
- Dementia and Cognitive Impairment Research
- RNA modifications and cancer
- Glaucoma and retinal disorders
- Chemotherapy-induced organ toxicity mitigation
- Corneal Surgery and Treatments
- Retinal Development and Disorders
- Genetics and Neurodevelopmental Disorders
- Metabolomics and Mass Spectrometry Studies
- Meat and Animal Product Quality
- Frailty in Older Adults
- Tryptophan and brain disorders
- Biochemical Acid Research Studies
- Animal Diversity and Health Studies
Mustafa Kemal University
2021-2024
Bezmiâlem Vakıf Üniversitesi
2023
University of California, Irvine
2008-2022
TOBB University of Economics and Technology
2014
UC Irvine Health
2013
Mitochondria Research and Medicine Society
2011
Pediatrics and Genetics
2005-2010
Cedars-Sinai Medical Center
2009
University of California, Irvine Medical Center
2009
Emory University
1998-2008
To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to peroxisome, nucleus, or mitochondria (MCAT). Median and maximum life spans were maximally increased (averages 5 months 5.5 months, respectively) MCAT animals. Cardiac pathology cataract development delayed, oxidative damage was reduced, H 2 O production -induced aconitase inactivation attenuated, mitochondrial deletions reduced. These results...
Oxidative stress has been implicated in many diseases. The chief source of reactive oxygen species within the cell is mitochondrion. We have characterized a variety biochemical and metabolic effects inactivation mouse gene for mitochondrial superoxide dismutase (CD1- Sod2 tm1Cje ). mutant mice exhibit tissue-specific inhibition respiratory chain enzymes NADH-dehydrogenase (complex I) succinate dehydrogenase II), tricarboxylic acid cycle enzyme aconitase, development urine organic aciduria...
Defects in mitochondrial oxidative phosphorylation have frequently been associated with Alzheimer's disease (AD), and both inherited somatic mtDNA mutations reported certain AD cases. To determine whether contribute more generally to the etiology of AD, we investigated sequence control region (CR) from brains for possible disease-causing mutations. Sixty-five percent harbored T414G mutation, whereas this mutation was absent all controls. Moreover, cloning sequencing CR patient revealed that...
To determine the importance of mitochondrial reactive oxygen species toxicity in aging and senescence, we analyzed changes function with age mice partial or complete deficiencies antioxidant enzyme manganese superoxide dismutase (MnSOD). Liver mitochondria from homozygous mutant mice, a deficiency MnSOD, exhibited substantial respiration inhibition marked sensitization permeability transition pore. Mitochondria heterozygous showed evidence increased proton leak, respiration, early rapid...
The majority of mitochondrial DNA (mtDNA) mutations that cause human disease are mild to moderately deleterious, yet many random mtDNA would be expected severe. To determine the fate more severe mutations, we introduced mtDNAs containing two affect oxidative phosphorylation into female mouse germ line. ND6 mutation was selectively eliminated during oogenesis within four generations, whereas milder COI retained throughout multiple generations even though offspring consistently developed...
Superoxide is produced as a result of normal energy metabolism within the mitochondria and scavenged by mitochondrial form superoxide dismutase (sod2). Mice with inactivated SOD2 (sod2 nullizygous mice) die prematurely, exhibiting several metabolic defects severe tissue pathologies, including lethal spongiform neurodegenerative disorder (Li et al., 1995; Melov 1998, 1999). We show that treatment sod2 mice synthetic (SOD)-catalase mimetics extends their lifespan threefold, rescues...
Increasing evidence is implicating mitochondrial dysfunction as a central factor in the etiology of Alzheimer's disease (AD). The most significant risk AD advanced age and an important neuropathological correlate deposition
Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function thought be central Mitochondrial dysfunction reduced secretion are also observed in β-cells of humans the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions chromosome 21 that may perturbed glucose homeostasis we profiled glycaemic status different DS mouse models. The...
purpose. To examine the mtDNA control regions in normal and age-related macular degeneration (AMD) retinas. identify variations associated with AMD. methods. Retinas from 10 11 AMD globes were isolated analyzed for rearrangements by long extension-polymerase chain reaction (LX-PCR) nature frequency of single-nucleotide polymorphisms (SNPs) region direct sequencing. Blood DNA was extracted 99 92 age-matched subjects. The sequence that define haplogroups H, I, J, K, T, V, X, U characterized...
Background Down's syndrome (DS) is the most common genetic cause of mental retardation. Reduced number and aberrant architecture dendritic spines are features DS neuropathology. However, mechanisms involved in spine alterations not known. In addition to a relevant role synapse formation maintenance, astrocytes can regulate dynamics by releasing soluble factors or physical contact with neurons. We have previously shown impaired mitochondrial function leading metabolic protein processing...
purpose. To determine whether keratoconus (KC) corneas have more mitochondrial (mt)DNA damage than do normal corneas. methods. Thirty-three and 34 KC were studied. Immunohistochemistry for mitochondria-encoded cytochrome c oxidase (complex IV) subunit 1 (CO-Ι) porins was performed. Total DNA isolated mtDNA genome amplified by either long-extension–polymerase chain reaction (LX-PCR) or short-extension–PCR (SX-PCR). LX-PCR digested with restriction enzymes to confirm full-length amplicon....
Genome-wide gene deregulation and oxidative stress appear to be critical factors determining the high variability of phenotypes in Down's syndrome (DS). Even though individuals with trisomy 21 exhibit a higher survival rate compared other aneuploidies, most them die utero or early during postnatal life. While survivors are currently predicted live past 60 years, they suffer incidence age-related conditions including Alzheimer's disease (AD). This paper is centered on mechanisms by which...
Mounting evidence implicates chronic oxidative stress as a critical driver of the aging process. Down syndrome (DS) is characterized by complex phenotype, including early senescence. DS cells display increased levels reactive oxygen species (ROS) and mitochondrial structural metabolic dysfunction, which are counterbalanced sustained Nrf2-mediated transcription cellular antioxidant response elements (ARE). Here, we show that caspase 3/PKCδdependent activation Nrf2 pathway in Dp16 (a mouse...
To determine mitochondrial (mt)DNA variants in AMD and age-matched normal retinas.Total DNA was isolated from retinas (AMD, n = 13; normal, 13), choroid 3), blood 138; 133). Long-extension-polymerase chain reaction amplified the full-length ( approximately 16.2 kb) mtDNA genome. Retinal sequenced for nucleotide length heteroplasmy. Pyrosequencing performed on heteroplasmic mtDNA. PCR amplification enzyme digestions were used to analyze changes.Retinal had a greater number of rearrangements...
We investigated the possible ameliorative effects of nobiletin (NBL) against methotrexate (MTX)-induced hepatorenal toxicity in rats. Twenty-eight Wistar albino rats were randomly divided into four groups, namely: Control; MTX (administered 20 mg/kg MTX); MTX+NBL and 10 NBL per day); mg/kg/day NBL). Histopathological, immunohistochemical biochemical analyses performed on kidney liver tissues at end study. caused renal toxicity, as indicated by increases malondialdehyde (MDA) caspase-3, well...
Abstract Prader–Willi syndrome (PWS) is a genetic disorder caused by deficiency of imprinted gene expression from the paternal chromosome 15q11–15q13 and clinically characterized neonatal hypotonia, short stature, cognitive impairment, hypogonadism, hyperphagia, morbid obesity, diabetes. Previous clinical studies suggest that defect in energy metabolism may be involved pathogenesis PWS. We focused our attention on genes associated with found there were 95 66 mitochondrial differentially...