ArticleNeurochemical research2016
Loss of SDHB Elevates Catecholamine Synthesis and Secretion Depending on ROS Production and HIF Stabilization.
Article in Neurochemical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production.BioMed research international · 2019Trial
- Genetic, cellular, and environmental factors influencing tumourigenesis in carriers of succinate dehydrogenase germline mutations.Endocrine-related cancer · 2026Review
- Case Report: The silent giant: biochemical-clinical dissociation in a large cystic pheochromocytoma.Frontiers in oncology · 2026Article
- Clinical significance, prognosis, and risk model of SDHB expression loss and ERBB2 expression in pheochromocytoma and paraganglioma.Endocrine connections · 2025Article
- TheInternational journal of molecular sciences · 2025Article
- SDH defective cancers: molecular mechanisms and treatment strategies.Cell biology and toxicology · 2025Review
- Characterisation of an Adult Zebrafish Model forInternational journal of molecular sciences · 2024Article
- The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy.Research (Washington, D.C.) · 2024Review
- Can Superoxide Anions Predict the Malignant Potential of Carotid body Tumor? - A Pilot Study.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2023Article
- Abdominal nonfunctional paraganglioma in which succinate dehydrogenase subunit B (SDHB) immunostaining was performed: a case report.Journal of medical case reports · 2023Article
- Succinate at the Crossroad of Metabolism and Angiogenesis: Roles of SDH, HIF1α and SUCNR1.Biomedicines · 2022Review
- Model systems in SDHx-related pheochromocytoma/paraganglioma.Cancer metastasis reviews · 2021Review
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- Hereditary pheochromocytoma/paraganglioma syndrome with a novel mutation in the succinate dehydrogenase subunit B gene in a Japanese family: two case reports.Journal of medical case reports · 2021Article
- Metabolic adaptation in hypoxia and cancer.Cancer letters · 2021Review
- Biological Mechanisms Induced by Soybean Agglutinin Using an Intestinal Cell Model of Monogastric Animals.Frontiers in veterinary science · 2021Article
- Redox Signaling from Mitochondria: Signal Propagation and Its Targets.Biomolecules · 2020Review
- Forms of selenium in vitamin-mineral mixes differentially affect the expression of genes responsible for prolactin, ACTH, and α-MSH synthesis and mitochondrial dysfunction in pituitaries of steers grazing endophyte-infected tall fescue.Journal of animal science · 2019Article
- Primary fibroblast co-culture stimulates growth and metabolism in Sdhb-impaired mouse pheochromocytoma MTT cells.Cell and tissue research · 2018Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Germline mutations in genes encoding succinate dehydrogenase subunits are associated with the development of familial pheochromocytomas and paragangliomas [hereditary paraganglioma/pheochromocytoma syndrome (HPPS)]. In particular, a mutation in succinate dehydrogenase subunit B (SDHB) is highly associated with abdominal paraganglioma and subsequent distant metastasis (malignant paraganglioma), indicating the importance of SDHB genetic testing. The discovery of HPPS suggests an association among genetic mitochondrial defects, tumor development, and catecholamine oversecretion. To investigate this association, we transfected pheochromocytoma cells (PC12) with SDHB-specific siRNA. SDHB silencing virtually abolished complex II activity, demonstrating the utility of this in vitro model for investigating the pseudo-hypoxic drive hypothesis. Lack of complex II activity resulting from RNA interference of SDHB increased tyrosine hydroxylase (TH; the rate-limiting enzyme in catecholamine biosynthesis) activity and catecholamine secretion. Reduced apoptosis was observed accompanied by Bcl-2 accumulation in PC12 cells, consistent with the phenotypes of paragangliomas with SDHB mutations. In addition, SDHB silencing increased reactive oxygen species (ROS) production and nuclear HIF1α stabilization under normoxic conditions. Furthermore, phenotypes induced by complex II activity knockdown were abolished by pretreatment with N-acetyl cysteine (an ROS scavenger) and by prior HIF1α knockdown, indicating an ROS- and HIF1α-dependent mechanism. Our results indicate that increased ROS may act as signal transduction messengers that induce HIF1α stabilization and may be necessary for the pseudo-hypoxic states observed in our experimental model. To our knowledge, this is the first study demonstrating that pseudo-hypoxic states resulting from SDHB knockdown are associated with increased TH activity and catecholamine oversecretion.
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