Karim Zuhra

ORCID: 0000-0003-0186-1817
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About
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Research Areas
  • Sulfur Compounds in Biology
  • Folate and B Vitamins Research
  • Amino Acid Enzymes and Metabolism
  • Cassava research and cyanide
  • Genomics, phytochemicals, and oxidative stress
  • Glutathione Transferases and Polymorphisms
  • Fibroblast Growth Factor Research
  • Neonatal Health and Biochemistry
  • Heme Oxygenase-1 and Carbon Monoxide
  • Alcohol Consumption and Health Effects
  • Polyamine Metabolism and Applications
  • Cancer, Hypoxia, and Metabolism
  • Mitochondrial Function and Pathology
  • Adenosine and Purinergic Signaling
  • Neuroscience of respiration and sleep
  • Adipose Tissue and Metabolism
  • Obstructive Sleep Apnea Research
  • Ferroptosis and cancer prognosis
  • Cancer Research and Treatments
  • Isotope Analysis in Ecology
  • Molecular Sensors and Ion Detection
  • Redox biology and oxidative stress
  • Natural Antidiabetic Agents Studies
  • Nutritional Studies and Diet
  • Nitric Oxide and Endothelin Effects

University of Fribourg
2020-2025

Sapienza University of Rome
2018-2021

Institute of Molecular Biology and Pathology
2018-2021

Universidade Nova de Lisboa
2018-2019

Latvijas Organiskās Sintēzes Institūts
2018

Instituto de Biologia Experimental e Tecnológica
2018

Abstract Small, gaseous molecules such as nitric oxide, carbon monoxide and hydrogen sulfide are produced signalling in mammalian cells. Here, we show that low concentrations of cyanide generated endogenously various tissues We detect several cellular compartments human cells the blood mice. Cyanide production is stimulated by glycine, occurs at pH lysosomes requires peroxidase activity. When a specific rate, exerts stimulatory effects on mitochondrial bioenergetics, cell metabolism...

10.1038/s42255-025-01225-w article EN cc-by Nature Metabolism 2025-03-03

Using a novel rat model of Down syndrome (DS), the functional role cystathionine-β-synthase (CBS)/hydrogen sulfide (H2S) pathway was investigated on pathogenesis brain wave pattern alterations and neurobehavioral dysfunction. Increased expression CBS subsequent overproduction H2S observed in DS rats, with primarily localizing to astrocytes vasculature. rats exhibited defects, accompanied by loss gamma activity suppression multiple pre- postsynaptic proteins. Aminooxyacetate, prototypical...

10.1016/j.redox.2022.102233 article EN cc-by-nc-nd Redox Biology 2022-01-13

Hydrogen sulfide (H2S) is an important endogenous gaseous transmitter mediator, which regulates a variety of cellular functions in autocrine and paracrine manner. The enzymes responsible for the biological generation H2S include cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) 3-mercaptopyruvate sulfurtransferase (3-MST). Increased expression these overproduction has been implicated essential processes various cancer cells, including stimulation metabolism, maintenance cell...

10.1016/j.phrs.2020.105393 article EN cc-by-nc-nd Pharmacological Research 2021-01-20

In mammalian cells, cyanide is viewed as a cytotoxic agent, which exerts its effects through inhibition of mitochondrial Complex IV (Cytochrome C oxidase [CCOx]). However, the current report demonstrates that cyanide’s effect on CCOx biphasic; low (nanomolar to low-micromolar) concentrations stimulate activity, while higher (high-micromolar) produce “classic” inhibitory effect. Low stimulated electron transport and elevated intracellular adenosine triphosphate (ATP), resulting in stimulation...

10.1073/pnas.2026245118 article EN cc-by Proceedings of the National Academy of Sciences 2021-05-10

Given the clinical, economic, and societal impact of obesity, unraveling mechanisms adipose tissue expansion remains fundamental significance. We previously showed that white (WAT) levels 3-mercaptopyruvate sulfurtransferase (MPST), a mitochondrial cysteine-catabolizing enzyme yields pyruvate sulfide species, are downregulated in obesity. Here, we report Mpst deletion results fat accumulation mice fed high-fat diet (HFD) through transcriptional metabolic maladaptation. Mpst-deficient on HFD...

10.1084/jem.20211894 article EN cc-by-nc-sa The Journal of Experimental Medicine 2022-05-26

Cystathionine beta-synthase (CBS) is a pivotal enzyme of the transsulfuration pathway responsible for diverting homocysteine to biosynthesis cysteine and production hydrogen sulfide (H2S). Aberrant upregulation CBS overproduction H2S contribute pathophysiology several diseases including cancer Down syndrome. Therefore, pharmacological inhibition has emerged as prospective therapeutic approach. Here, we characterized binding inhibitory mechanism aminooxyacetic acid (AOAA), most commonly used...

10.1007/s00018-022-04479-9 article EN cc-by Cellular and Molecular Life Sciences 2022-07-21

Down syndrome (DS) is a genetic condition where the person born with an extra chromosome 21. DS associated accelerated aging; people are prone to age-related neurological conditions including early-onset Alzheimer's disease. Using Dp(17)3Yey/ + mice, which overexpresses portion of mouse 17, encodes for transsulfuration enzyme cystathionine β-synthase (CBS), we investigated functional role CBS/hydrogen sulfide (H

10.1007/s11357-024-01146-8 article EN cc-by GeroScience 2024-04-01

Hydrogen sulfide (H 2 S), a known inhibitor of cytochrome c oxidase (CcOX), plays key signaling role in human (patho)physiology. H S is synthesized endogenously and mainly metabolized by mitochondrial sulfide-oxidizing pathway including sulfide:quinone oxidoreductase (SQR), whereby S-derived electrons are injected into the respiratory chain stimulating O consumption ATP synthesis. Under hypoxic conditions, has higher stability at levels with protective effects for cell. Herein, working on...

10.1155/2019/8102936 article EN Oxidative Medicine and Cellular Longevity 2019-01-29

Recently, a CRISPR-Cas9 genome-editing system was developed with introduced sequential 'driver' mutations in the WNT, MAPK, TGF-β, TP53 and PI3K pathways into organoids derived from normal human intestinal epithelial cells. Prior studies have demonstrated that isogenic harboring tumor suppressor genes APC, SMAD4 TP53, as well oncogene KRAS, assumed more proliferative invasive properties vitro vivo. A separate body of implicates role various hydrogen sulfide (H2S)-producing enzymes...

10.3390/antiox11091823 article EN cc-by Antioxidants 2022-09-15

Hydrogen sulfide (H2S) is an endogenously produced signaling molecule. The enzymes 3-mercaptopyruvate sulfurtransferase (MST), partly localized in mitochondria, and the inner mitochondrial membrane-associated sulfide:quinone oxidoreductase (SQR), besides being respectively involved synthesis catabolism of H2S, generate sulfane sulfur species such as persulfides polysulfides, currently recognized mediating some H2S biological effects. Reprogramming metabolism was reported to support cellular...

10.3390/cells8080828 article EN cc-by Cells 2019-08-04

Hydrogen sulfide (H2S) is an endogenous mammalian gasotransmitter. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) are the principal enzymes responsible for its biogenesis. A recent yeast screen suggested that disulfiram (a well-known inhibitor of aldehyde dehydrogenase a clinically used drug in treatment alcoholism) may inhibit CBS cell-based environment. However, prior studies have not observed any direct inhibition by...

10.1016/j.bcp.2020.114267 article EN cc-by-nc-nd Biochemical Pharmacology 2020-10-07

Despite recent advances in melanoma treatment, there are still patients that either do not respond or develop resistance. This unresponsiveness and/or acquired resistance to therapy could be explained by the fact some cells reside a dedifferentiated state. Interestingly, this state is associated with greater sensitivity ferroptosis, lipid peroxidation-reliant, iron-dependent form of cell death. Cytoglobin (CYGB) an iron hexacoordinated globin highly enriched melanocytes and frequently...

10.3390/antiox11081548 article EN cc-by Antioxidants 2022-08-10

Cystathionine β-synthase (CBS), CSE (cystathionine γ-lyase) and 3-mercaptopyruvate sulfurtransferase (3-MST) have emerged as three significant sources of hydrogen sulfide (H2S) in various forms mammalian cancer. Here, we investigated the functional role CBS’ 3-MST’s catalytic activity murine breast cancer cell line EO771. The CBS/CSE inhibitor aminooxyacetic acid (AOAA) 3-MST 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE) were used to assess endogenous...

10.3390/antiox12030647 article EN cc-by Antioxidants 2023-03-05

Abstract H 2 S is generated in the adipose tissue by cystathionine γ-lyase, β-synthase, and 3-mercaptopyruvate sulfurtransferase (3-MST). plays multiple roles regulation of various metabolic processes, including insulin resistance. biosynthesis also occurs adipocytes. Aging known to be associated with a decline S. Therefore, question arises whether endogenous deficiency may affect process adipocyte maturation lipid accumulation. Among three S-generating enzymes, role 3-MST least understood...

10.1007/s11357-022-00600-9 article EN cc-by GeroScience 2022-06-10

Epigallocatechin gallate (EGCG) is the main bioactive component of green tea. Through screening a small library natural compounds, we discovered that EGCG inhibits cystathionine β-synthase (CBS), major H2S-generating enzyme. Here characterize EGCG's mechanism action in context CBS-derived H2S production. In current project, biochemical, pharmacological and cell biology approaches were used to effect on CBS cellular models cancer Down syndrome (DS). The results show binds H2S-producing...

10.1016/j.niox.2022.07.007 article EN cc-by Nitric Oxide 2022-08-13

The ‘gasotransmitters’ hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO) act as second messengers in human physiology, mediating signal transduction via interaction with or chemical modification of protein targets, thereby regulating processes such neurotransmission, blood flow, immunomodulation, energy metabolism. Due to their broad reactivity potential toxicity, the biosynthesis breakdown H2S, NO, CO are tightly regulated. Growing evidence highlights active role...

10.3390/antiox10091391 article EN cc-by Antioxidants 2021-08-30

Abstract Biosynthesis of hydrogen sulfide (H 2 S), a key signalling molecule in human (patho)physiology, is mostly accomplished by the enzymes cystathionine β-synthase (CBS), γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MST). Several lines evidence have shown close correlation between increased H S production diseases, such as several cancer types amyotrophic lateral sclerosis. Identifying compounds selectively potently inhibiting S-synthesizing may therefore prove beneficial for...

10.1038/s41598-018-36994-w article EN cc-by Scientific Reports 2019-01-24

Abstract Small, gaseous molecules, known as gasotransmitters (NO, CO, H 2 S), are produced endogenously in mammalian cells and serve important biological roles. Hydrogen cyanide, traditionally considered a cytotoxic molecule mammals, serves an endogenous mediator several plants bacterial species. Here we show that low concentrations of cyanide generated mouse liver human hepatocytes. Cyanide production is stimulated by glycine, occurs at the pH lysosomes requires peroxidase activity....

10.1101/2024.06.03.597146 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-06-03
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