Publications by authors named "Fatimah Al Khazal"
Article Synopsis
- Loss of heterozygosity for defective alleles of the SDH enzyme can lead to paragangliomas, a type of tumor originating in neuroendocrine cells in humans.
- Researchers created mouse models with conditional loss of the SDHC subunit in early development, hypothesizing it would induce paraganglioma in chromaffin cells.
- Instead of tumors, mice showed developmental defects like gait anomalies and fur discoloration, indicating neural crest cell dysfunction without tumor formation, suggesting differences between human and mouse responses to SDH loss.
Mutations in any of the genes encoding the four subunits of succinate dehydrogenase (SDH), a mitochondrial membrane-bound enzyme complex that is involved in both the tricarboxylic acid cycle and the electron transport chain, can lead to a variety of disorders. Recognized conditions with such mutations include Leigh syndrome and hereditary tumors such as pheochromocytoma and paraganglioma (PPGL), renal cell carcinoma, and gastrointestinal stromal tumor. Tumors appear in SDH mutation carriers with dominant inheritance due to loss of heterozygosity in susceptible cells.
View Article and Find Full Text PDFLeigh syndrome embodies degenerative disorders with a collection of symptoms secondary to inborn errors of metabolism. Combinations of hypomorphic and loss-of-function alleles in many genes have been shown to result in Leigh syndrome. Interestingly, deficiency for the tricarboxylic acid cycle enzyme succinate dehydrogenase (SDH) can lead to Leigh-like syndrome in some circumstances and to cancer (paraganglioma, renal cell carcinoma, gastrointestinal stromal tumor) in others.
View Article and Find Full Text PDFAn Amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFActivated CD4 T cells proliferate rapidly and remodel epigenetically before exiting the cell cycle and engaging acquired effector functions. Metabolic reprogramming from the naive state is required throughout these phases of activation. In CD4 T cells, T-cell-receptor ligation-along with co-stimulatory and cytokine signals-induces a glycolytic anabolic program that is required for biomass generation, rapid proliferation and effector function.
View Article and Find Full Text PDFArticle Synopsis
- Succinate dehydrogenase (SDH) loss in pheochromocytoma and paraganglioma tumors disrupts normal cellular metabolism, leading to increased succinate levels that activate cancer-related pathways but the exact mechanisms remain unclear.
- Researchers created a specific mouse cell line to study how SDH loss affects gene rearrangement, protein expression, and cell growth, while also comparing changes at the transcriptomic, epigenomic, and proteomic levels.
- The study found that cells with SDH loss are particularly sensitive to the inhibition of lactate dehydrogenase A (LDHA), indicating potential for LDHA-targeted therapies in treating these types of tumors.
Article Synopsis
- Diabetic gastroparesis often involves a depletion of interstitial cells of Cajal (ICCs), while some diabetic patients experience accelerated gastric emptying (GE), especially when accompanied by obesity and high blood glucose levels.
- Research using mutant mice revealed that hyperglycemia led to increased proliferation of ICCs and faster GE, possibly due to enhanced signaling pathways involving MAPK1 and MAPK3.
- Various experimental methods, including breath tests and genetic manipulation, were used to analyze the effects of hyperglycemia on ICCs and their role in gastric motility.