Cell and Developmental Biology Commons^™

A Conserved Role For Cyclin C In Regulated Cell Death Across Yeast And Humans, Samar Emami, David Stieg, Daniel Smethurst, Justin Bauer, Randy Strich

Rowan-Virtua Research Day

Background: Programmed cell death (PCD) is a tightly regulated process that maintains tissue homeostasis and eliminates damaged, infected, or malignant cells. A key regulator of this process is Cyclin C (CCNC), which functions as a component of the mediator complex to regulate gene transcription. During cellular stress, CCNC translocates from the nucleus to the mitochondria, where it associates with Dnm1 to promote mitochondrial fragmentation and  apoptosis.

Objective: This study aimed to unravel conservation of CCNC’s function between yeast and humans by investigating whether human CCNC can induce apoptosis in yeast and whether it does so through interaction with …

Disrupted Nuclear Function And Nucleocytoplasmic Transport In Parkinson’S Disease, Ichiro M. Matoba

The Cardinal Edge

No abstract provided.

An Antioxidant Cocktail Of Tert-Butylhydroquinone And A Manganese Porphyrin Induces Toxic Levels Of Oxidative Stress In Cancer Cells, Sandra Tamarin, Hannah Jung, Joseph Lamorte, Laura Biesterveld, Gabriel Piñero, Grace Turchetta, Molly Myers, Rebecca Oberley-Deegan, Aimee Eggler

Student Papers, Posters & Projects

Despite significant advancement in cancer treatments, therapies with minimal toxicity to healthy cells are still limited. One targetable weakness of cancer cells is their sensitivity to oxidative stress. We find that the combination of two antioxidants—the common food additive tert-butylhydroquinone (tBHQ) and a manganese porphyrin in clinical trials, MnTnBuOE-2-PyP5+ (MnBuOE)—increases oxidative stress and causes apoptotic death in several cancer cell lines, but not in mouse primary fibroblasts. Investigating the mechanism of cell death, MnBuOE is observed to catalyze the oxidation of tBHQ, producing the electrophilic quinone tert-butylquinone (tBQ). A critical role for tBQ and its electrophilic character was revealed with …

Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici

Honors Undergraduate Theses

Manuka honey is known for its vital usage in wound healing, being an agonist towards fighting infections, and is an acting antioxidant [32]. Its main constituents are flavonoids and phenolic compounds, with methyl syringate (MSYR) being a major active ingredient. The specific compounds responsible for these antioxidant effects, particularly in the CNS, remain unclear. It is hypothesized that pre-treatment of mouse neuroblastoma cells with MSYR followed by hydrogen peroxide exposure will activate the AMPK/SIRT1/PGC-1a pathway, due to MSYR’s phenolic structure, and thus reduce oxidative stress and improve mitochondrial biogenesis. Hydrogen peroxide is a standard reactive oxygen species (ROS) treatment to …

Brief Pulses Of High-Level Fluid Shear Stress Enhance Metastatic Potential And Rapidly Alter The Metabolism Of Cancer Cells, Amanda N. Pope, Devon L. Moose, Guy O. Hudson, Hank R. Weresh, Marion R. Dykstra, Aabha Y. Joshi, Patrick Breheny, Eric B. Taylor, Michael D. Henry

Department of Biomedical and Translational Sciences Faculty Publications

Circulating tumor cells (CTCs) face challenges to their survival, including mechanical and oxidative stresses that are different from cancer cells in solid primary and metastatic tumors. The impact of adaptations to the fluid microenvironment of the circulation on the outcome of the metastatic cascade is not well understood. Here, we find that cancer cells exposed to brief pulses of high-level fluid shear stress (FSS) exhibit enhanced invasiveness and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo. Cancer cells exposed to FSS rapidly alter their metabolism in a manner that promotes survival by providing energy for cytoskeletal remodeling …

Modulation Of Redox-Sensitive Cardiac Ion Channels, Rawan S. Orfali, Al Hassan Gamal El-Din, Varnika Karthik, Elisanjer Lamis, Vanna Xiao, Alena Ramanishka, Abdullah Alwatban, Osama Alkhamees, Ali Alaseem, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate …

Mechanisms Of Placental Impairment And The Upregulation Of Fetuin-B During Maternal Undernourishment, Mia Camilliere

NYMC Student Theses and Dissertations

Proper nutrition is crucial during pregnancy to support fetal and placental development. Failure to meet these nutritional needs can result in adverse health outcomes for both mother and baby. Despite its high prevalence in underdeveloped countries, maternal undernourishment is a public health issue worldwide. There are several possible causes of maternal undernourishment, and these can occur alone or in combination, such as poor access to nutrition, hyperemesis gravidarum, and drug use. This condition can adversely affect placental development and function to the extent of placental insufficiency, perturbing the entire pregnancy. The placenta is responsible not only for hormonally and physically …

The Relationship Between Oxidative Stress And Partner Opposition In Conflict Resolution, Jenna Thomas

Biological Sciences Undergraduate Honors Theses

Given the inevitability of conflict in romantic relationships, understanding its biological impact is crucial for developing conflict resolution strategies that promote physical health. While many studies highlight relationship conflict’s negative effects on bodily systems, few examine how specific facets of conflict, such as opposition, impact the body. Partner opposition may contribute to oxidative stress, a biological marker associated with poor physical health, by activating the amygdala. This study investigated the association between partner opposition and oxidative stress in 126 couples expecting their first child. Participants attended a lab session where problem-solving discussions were recorded to assess oppositional behavior and urine …

Repositioning Antimalarial Drugs As Anticancer Agents: Focus On Tafenoquine, Chris Barton

Funded Scholarship

Due to the expensive and lengthy process of drug design and approval, drug repurposing (or repositioning) has become another option for identifying preexisting molecules that may be used for alternative purposes. Recently, some antimalarial compounds have been shown to display efficacy against cancer cell proliferation. In this study, we provide evidence to suggest that multiple preexisting antimalarial drugs can reduce the viability of human cancer cells in culture. Furthermore, we provide the first evidence that one antimalarial, Tafenoquine (LD50 = 9.6 μM in HCT116 cells), is capable of decreasing viability with an efficacy comparable to Etoposide (LD50 = 15.2 μM …

Stanniocalcin 2 Governs Cancer Cell Adaptation To Nutrient Insufficiency Through Alleviation Of Oxidative Stress, Shuo Qie, Haijuan Xiong, Yaqi Liu, Chenhui Yan, Yalei Wang, Lifeng Tian, Chenguang Wang, Nianli Sang

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial nutrient insufficiency remains unclear. We previously identified STC2 as one of the most upregulated genes in cells exposed to nutrient insufficiency by transcriptome screening, indicating the potential of STC2 in cellular adaptation to nutrient insufficiency. However, the molecular mechanisms underlying STC2 induction by nutrient insufficiency and subsequent adaptation remain elusive. Here, we report that STC2 protein is dramatically increased and secreted into the culture media by Gln-/Glc- deprivation. STC2 promoter contains cis-elements that are activated by ATF4 and p65/RelA, two transcription factors activated by …

Diesel Exhaust Particles Alter Mitochondrial Bioenergetics And Camp Producing Capacity In Human Bronchial Epithelial Cells, Isabella Cattani-Cavalieri, Marina Trombetta-Lima, Hong Yan, Ana L. Manzano-Covarrubias, Hoeke A. Baarsma, Asmaa Oun, Melissa Mol Van Der Veen, Emily Oosterhout, Amalia M. Dolga, Rennolds S. Ostrom, Samuel Santos Valenca, Martina Schmidt

Pharmacy Faculty Articles and Research

Introduction: Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis. The impact of DEP on cAMP signaling is largely unknown.

Methods: We exposed human bronchial epithelial (BEAS-2B) cells to DEP for 24–72 h and evaluated mitochondrial bioenergetics, markers of oxidative stress and inflammation and the components of cAMP signaling. Mitochondrial bioenergetics was measured at 72 h to capture the potential and accumulative effects of …

Ceramide-Mediated Orchestration Of Oxidative Stress Response Through Filopodia-Derived Small Extracellular Vesicles, Zainuddin Quadri, Ahmed Elsherbini, Simone M. Crivelli, Salim S. El-Amouri, Priyanka Tripathi, Zhihui Zhu, Xiaojia Ren, Liping Zhang, Stefka D. Spassieva, Mariana N. Nikolova‑Karakashian, Erhard Bieberich

Markey Cancer Center Faculty Publications

Extracellular vesicles (EVs) are shed from the plasma membrane, but the regulation and function of these EVs remain unclear. We found that oxidative stress induced by H 2 O 2 in Hela cells stimulated filopodia formation and the secretion of EVs. EVs were small (150 nm) and labeled for CD44, indicating that they were derived from filopodia. Filopodia-derived small EVs (sEVs) were enriched with the sphingolipid ceramide, consistent with increased ceramide in the plasma membrane of filopo- dia. Ceramide was colocalized with neutral sphingomyelinase 2 (nSMase2) and acid sphingomyelinase (ASM), two sphingomyelinases generating ceramide at the plasma membrane. Inhibition of …

Mir-200c Reprograms Fibroblasts To Recapitulate The Phenotype Of Cafs In Breast Cancer Progression, Zhao Lin, Megan Roche, Víctor Díaz-Barros, Marina Domingo-Vidal, Diana Menezes, Madalina Tuluc, Guldeep Uppal, Jaime Caro, Joseph Curry, Ubaldo Martinez-Outshoorn

Kimmel Cancer Center Faculty Papers

Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces a senescent phenotype. This pro-tumorigenic profile in CAFs fosters carcinoma …

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …

Naturally Derived Phenethyl Isothiocyanate Modulates Induction Of Oxidative Stress Via Its N-Acetylated Cysteine Conjugated Form In Malignant Melanoma, Sotiris Kyriakou, Nikoletta Demosthenous, Tom Amery, Kyle J. Stewart, Paul G. Winyard, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Phenethyl isothiocyanate (PEITC) is a secondary metabolic product yielded upon the hydrolysis of gluconasturtiin and it is highly accumulated in the flowers of watercress. The aim of the current study was to assess the role of a naturally derived PEITC-enriched extract in the induction of oxidative stress and to evaluate its anti-melanoma potency through the regulation of its metabolism with the concurrent production of the N-acetyl cysteine conjugated by-product. For this purpose, an in vitro melanoma model was utilized consisting of human primary (A375) cells as well as metastatic (COLO-679) malignant melanoma cells together with non-tumorigenic immortalized keratinocytes (HaCaT). …

Multiple Variables Influence The Finely Calibrated Antioxidant Defenses Of Clostridioides Difficile, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The obligate anaerobe Clostridioides difficile encodes multiple reductases to detoxify molecular oxygen and reactive oxygen species. Caulat and colleagues have characterized the activity and regulation of four such reductases (L. C. Caulat, A. Lotoux, M. C. Martins, N. Kint, et al., mBio 15:e01591-24, 2024, https://doi.org/10.1128/mbio.01591-24). Each proved critical for clostridial survival in a different range of oxygen concentrations; together, they ameliorate a broad range of oxidative stress levels. Moreover, two previously uncharacterized regulators were found to control reductase gene expression in response to oxidative stress. The genetic repressor Rex and the reductase FdpF are both sensitive to the NAP …

Cell-Based Screening Of Antistress Activity Of Some Phytochemicals: Identification, Validation, And Relevance To Old-Age Related Pathologies, Huayue Zhang, Sunil Kaul, Renu Wadhwa

Research Symposium

Background: A variety of environmental stresses have been shown to contribute to poor quality of life, tissue dysfunctions and ailments including metabolic disorders, cognitive impairment, and accelerated aging. Oxidative stress (an imbalance between the production and processing of highly reactive oxygen species) is largely associated with these phenotypes. Whereas drug development and disease therapeutics have advanced remarkably in last three decades, there are still limited options for stress management. Since the later can effectively decrease the disease burden, we aimed to screen phytochemicals with anti-oxidative stress activity using cell-based assays.

Methods: Brain-derived cells were subjected to chemical models of oxidative …

Novel Roles Of The Blm Syndrome Dna Helicase In Genome Maintenance And Mitochondrial Regulation, Brian B. Rodemoyer

USF Tampa Graduate Theses and Dissertations

Bloom syndrome (BS) is an extremely rare autosomal recessive genetic disorder caused by defects in the BLM gene. Patients with BS display a broad phenotypic spectrum including abnormally short stature, microcephaly, sun sensitivity, insulin resistance, perpetual oxidative stress, and a ~300-fold greater propensity for developing cancer than the general population. As such, BS patients typically do not live past their 20’s. The BLM gene encodes the BLM helicase, a member of the highly conserved RecQ family of 3’ to 5’ DNA helicases. Most of our cellular understanding of BLM is through its role in DNA damage repair through the homologous …

Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei

Markey Cancer Center Faculty Publications

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …

Endogenous Antioxidant Response And Lipid Peroxidation Levels In Muscle Tissue Of The Cownose Ray (Rhinoptera Bonasus), Bailey Berry

College of Graduate Studies: Theses & Dissertations

Oxidative stress is the result of an imbalance between reactive oxygen species (ROS) and antioxidant response within cells. ROS generation is a natural consequence of ETC activity within the mitochondria and is associated with aerobic metabolism. Oxidative stress data on elasmobranch muscle is limited, with previous studies primarily focusing on mammalian and teleost muscle. Elasmobranch skeletal muscle is generally composed of large proportions of white muscle fibers (anaerobic), low proportions of red muscle fibers (aerobic), and low proportions of pink muscle fibers (anaerobic). The cownose ray, a benthopelagic batoid species, presents an interesting model of study because it contains relatively …

Roles Of Oxidative Stress And Dna Methylation In Cigarette Smoking-Induced Accelerated Acute Myeloid Leukemia Progression, Mary Figueroa

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a commonly diagnosed cancer in smokers. When current or former smokers have AML, they have worse survival compared to never smoking patients. This has been observed clinically for decades, but then it is unknown how smoking leads to worsened AML survival. Smoking causes oxidative stress and altered DNA methylation that persists for decades in peripheral blood mononuclear cells, but these changes from smoking have not been evaluated in the context of AML. We hypothesize that smoking-induced molecular changes, including altered DNA methylation associated with poor AML prognosis, promote AML. We developed a novel model to …

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov

Chemistry & Biochemistry Faculty Publications

n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds …

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …

Deoxyribose Phosphate Aldolase Is Required For Development Of Hematopoietic Stem Cells In The Zebrafish Embryo, Anubhav Thapaliya, Sanyam Patel, Teerth Y. Patel, Sivam J. Bhatt, Erich W. Damm

Undergraduate Research Posters

Hematopoietic stem cells (HSCs) are an integral part of modern biomedical research because they are precursors to all blood cell lineages in vertebrates. Further understanding of hematopoietic development will allow for improvements in the success of therapeutic bone marrow transplantation; which is a crucial treatment in management of both malignant and non-malignant blood disorders. Although HSC transplantation is curative for many blood disorders, finding compatible donors is difficult due to a need for immunologic compatibility. Consequently, recent research efforts have been directed towards generating HSCs for the patient, from the patient themselves through the directed differentiation of induced pluripotent stem …

Salicylic Acid: A Key Regulator Of Redox Signalling 1 And Plant Immunity, Mohd Saleem, Qazi Fariddudin, Christian Castroverde

Biology Faculty Publications

In plants, the reactive oxygen species (ROS) formed during normal conditions are essential in regulating several processes, like stomatal physiology, pathogen immunity and developmental signaling. However, biotic and abiotic stresses can cause ROS over-accumulation leading to oxidative stress. Therefore, a suitable equilibrium is vital for redox homeostasis in plants, and there have been major advances in this research arena. Salicylic acid (SA) is known as a chief regulator of ROS; however, the underlying mechanisms remain largely unexplored. SA plays an important role in establishing the hypersensitive response (HR) and systemic acquired resistance (SAR). This is underpinned by a robust and …

Unbiased Automated Quantitation Of Ros Signals In Live Retinal Neurons Of Drosophila Using Fiji/Imagej, Prajakta Deshpande, Neha Gogia, Anuradha Venkatakrishnan Chimata, Amit Singh

Biology Faculty Publications

Numerous imaging modules are utilized to study changes that occur during cellular processes. Besides qualitative (immunohistochemical) or semiquantitative (Western blot) approaches, direct quantitation method(s) for detecting and analyzing signal intensities for disease(s) biomarkers are lacking. Thus, there is a need to develop method(s) to quantitate specific signals and eliminate noise during live tissue imaging. An increase in reactive oxygen species (ROS) such as superoxide (O2•-) radicals results in oxidative damage of biomolecules, which leads to oxidative stress. This can be detected by dihydroethidium staining in live tissue(s), which does not rely on fixation and helps prevent stress on tissues. However, …

The Interconnectivity Of Parkinson's Disease And Type Two Diabetes Mellitus, Erica Olfson

Honors Scholars Collaborative Projects

This thesis is about the biochemical connection between Parkinson's disease and Type II Diabetes Mellitus.

Herbal Extracts As Neuroprotective Agents In An In-Vitro Model Of Aluminum Neurotoxicity, Nada Ezzelarab

Theses and Dissertations

Background: Aluminum toxicity due to environmental or industrial exposure, medical applications, or from cooking utensils is a serious medical problem. The current study aims to investigate three herbal extracts: pomegranate peel extract, Achillea fragrantissima extract, and papaya fruit extract to combat this neurotoxicity.

Methods: Chemical characterization of the three extracts were evaluated using HPLC MS while their neuroprotective activity was assayed using MTT assay on SHSY5Y cells and nitric oxide levels.

Results: Using HPLC-MS chromatography, we have identified twenty-one compounds in the hydro-alcoholic Achillea fragrantissima, seventeen were determined in the pomegranate peel, eleven were assessed in the Carica papaya …

Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber

Senior Honors Theses

The improved survival rate for pediatric cancer patients is one of the greatest triumphs of recent medicine, but the late effects faced by these survivors have been uncovered through this new population of survivors. Many survivors of pediatric acute lymphoblastic leukemia (ALL) experience cognitive deficits in areas such as attention, memory, processing speed, and academic achievement following cancer treatment. Recent research has pointed to chemotherapeutic agents, host risk factors, and genetic predispositions as perpetrators of these deficits, although other factors are also under investigation. Consequently, the search for appropriate interventions for the amelioration of these deficits has dominated the literature …

Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog

Wayne State University Dissertations

The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …