LDH isozymes were assayed by polyacrylamide gel electrophoresis in 6 long-term transplantable skin tumours in Syrian hamsters. The percentages of the M-subunits were as follows: in a slow growing fibrosarcoma with abortive differentiation and producing lung metastases -- 63.3; in two well differentiated squamous cell carcinomas with moderate growth -- 79.8 and 74.9; in a slow growing and metastasizing melanotic melanoma -- 67.7; in undifferentiated amelanotic and depigmented melanomas with very fat growth -- 72.8 and 77.4. Therefore no consistent relationship has emerged between histogenesis, growth rate, differentiation and metastases of the studied neoplasms from one side and their LDH isozyme pattern -- on the other.
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Nano Lett
January 2025
School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, China.
To explore the intergenerational cardiotoxicity of nanoplastics, maternal mice were exposed to 60 nm polystyrene nanoplastics (PS-NP) during pregnancy and lactation. The results showed that PS-NP can enter the hearts of offspring and induce myocardial fiber arrangement disorder, acidophilic degeneration of cardiomyocytes, and elevated creatine kinase isoenzymes (CK-MB) and lactate dehydrogenase (LDH) levels after maternal exposure to PS-NP at 100 mg/kg during pregnancy and lactation. Mechanistically, KEGG analysis of RNA sequencing showed the participation of hypoxia-inducible factor-1 (HIF-1) and ferroptosis in PS-NP-induced cardiotoxicity.
View Article and Find Full Text PDFKorean J Physiol Pharmacol
January 2025
Department of Physiology, Ajou University School of Medicine, Suwon 16499, Korea.
The brain's substantial metabolic requirements, consuming a substantial fraction of the body's total energy despite its relatively small mass, necessitate sophisticated metabolic mechanisms for efficient energy distribution and utilization. The astrocyte-neuron lactate shuttle (ANLS) hypothesis has emerged as a fundamental framework explaining the metabolic cooperation between astrocytes and neurons, whereby astrocyte-derived lactate serves as a crucial energy substrate for neurons. This review synthesizes current understanding of brain energy metabolism, focusing on the dual roles of lactate as both an energy substrate and a signaling molecule.
View Article and Find Full Text PDFCell Death Differ
December 2024
Department of General Thoracic Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
Ferroptosis is an oxidative, non-apoptotic cell death frequently inactivated in cancer, but the underlying mechanisms in oncogene-specific tumors remain poorly understood. Here, we discover that lactate dehydrogenase (LDH) B, but not the closely related LDHA, subunits of active LDH with a known function in glycolysis, noncanonically promotes ferroptosis defense in KRAS-driven lung cancer. Using murine models and human-derived tumor cell lines, we show that LDHB silencing impairs glutathione (GSH) levels and sensitizes cancer cells to blockade of either GSH biosynthesis or utilization by unleashing KRAS-specific, ferroptosis-catalyzed metabolic synthetic lethality, culminating in increased glutamine metabolism, oxidative phosphorylation (OXPHOS) and mitochondrial reactive oxygen species (mitoROS).
View Article and Find Full Text PDFEur J Med Chem
February 2025
Korean Medical Research Center for Healthy Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea; Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Electronic address:
Inhibition of lactate dehydrogenase (LDH) has emerged as a promising cancer therapy strategy due to its essential role in the metabolic transformation of cancer cells. In this study, 53 derivatives of 1-hydroxy(and 1-alkoxy, 1-acyloxy)indoles were designed, synthesized, and biologically evaluated. Several multi-substituted 1-hydroxy(and 1-alkoxy, 1-acyloxy)indole compounds exhibited inhibitory activity against the LDH-A isoform (LDHA).
View Article and Find Full Text PDFExp Neurol
February 2025
Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea. Electronic address:
Neurons' high energy demands for processing, transmitting, and storing information in the brain necessitate efficient energy metabolism to maintain normal neuronal function. The astrocyte-neuron lactate shuttle (ANLS) hypothesis suggests neurons preferentially use lactate from astrocytes over glucose for energy. This study investigated lactate dehydrogenase B (LDHB), which preferentially converts lactate to pyruvate, in neuronal energy metabolism and cognitive function.
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