A5016813005- Cell death mechanisms and regulation
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- RNA Research and Splicing
- Organ Transplantation Techniques and Outcomes
- Circular RNAs in diseases
- Hemoglobin structure and function
- Renal and related cancers
- Heme Oxygenase-1 and Carbon Monoxide
- Autophagy in Disease and Therapy
- Ion channel regulation and function
- interferon and immune responses
- Pancreatic function and diabetes
- Chronic Kidney Disease and Diabetes
- Advanced Glycation End Products research
- Neuroblastoma Research and Treatments
- Diet, Metabolism, and Disease
- Electrolyte and hormonal disorders
- PARP inhibition in cancer therapy
- Birth, Development, and Health
- Ion Transport and Channel Regulation
- MicroRNA in disease regulation
University of South Australia
2014-2021
South Australia Pathology
2017-2021
Centre for Cancer Biology
2014-2021
Flinders Medical Centre
2011
Flinders University
2011
Abstract Caspase-2 has been shown to be involved in metabolic homeostasis. Here, we show that caspase-2 deficiency alters basal energy metabolism by shifting the balance fuel choice from fatty acid carbohydrate usage. At 4 weeks of age, whole-body utilisation was increased Casp2 −/− mice and maintained into adulthood. By 17 had reduced white adipose mass, smaller adipocytes decreased fasting blood glucose plasma triglycerides but normal insulin levels. When placed on a 12-week high-fat diet...
Ageing is a complex biological process for which underlying biochemical changes are still largely unknown. We performed comparative profiling of the cellular proteome and metabolome to understand molecular basis ageing in Caspase-2-deficient (Casp2(-/-)) mice that model premature absence overt disease. Age-related were determined liver serum young (6-9 week) aged (18-24 month) wild-type Casp2(-/-) mice. identified perturbed metabolic pathways, decreased levels ribosomal respiratory proteins...
Aberrant cell death/survival has a critical role in the development of hepatocellular carcinoma (HCC). Caspase-2, death protease, limits oxidative stress and chromosomal instability. To study its reactive oxygen species (ROS) DNA damage-induced liver cancer, we assessed diethylnitrosamine (DEN)-mediated tumour caspase-2-deficient (Casp2−/−) mice. Following DEN injection young animals, was monitored for 10 months. We found that DEN-treated Casp2−/− mice have dramatically elevated burden...
Abstract Kidney disease progression can be affected by Na + abundance. A key regulator of homeostasis is the ubiquitin ligase NEDD4-2 and its deficiency leads to increased transport activity salt-sensitive progressive kidney damage. However, mechanisms responsible for high induced damage remain poorly understood. Here we show that a diet compromised function in Nedd4-2 -deficient mice, indicative toward end-stage renal disease. Injury was characterized enhanced tubule dilation extracellular...
Caspase-2 has been implicated in various cellular functions, including cell death by apoptosis, oxidative stress response, maintenance of genomic stability and tumor suppression. The loss the caspase-2 gene (Casp2) enhances oncogene-mediated tumorigenesis induced E1A/Ras athymic nude mice, also Eμ-Myc lymphoma MMTV/c-neu mammary mouse models. To further investigate function tumorigenesis, we extended our studies TH-MYCN transgenic model neuroblastoma. Surprisingly, found that delayed...
Abstract Gender-specific differences are commonly found in metabolic pathways and response to nutritional manipulation. Previously, we identified a role for caspase-2 age-related glucose homeostasis lipid metabolism using male -deficient ( Casp2 −/− ) mice. Here show that the resistance age-induced tolerance does not occur female mice it appears be independent of insulin sensitivity males. Using fasting (18 h) as means further investigate energy metabolism, sex-specific mobilization. In aged...
Abstract Salt homeostasis is maintained by tight control of Na + filtration and reabsorption. In the distal part nephron ubiquitin protein ligase Nedd4-2 regulates membrane abundance thus activity epithelial channel (ENaC), which rate-limiting for deficiency in mouse results elevated ENaC nephropathy, however contribution dietary salt to this has not been characterized. study we show that high exacerbated kidney injury -deficient mice, significantly perturbing normal postnatal nephrogenesis...
Abstract Caspase-2 is a highly conserved cysteine protease with roles in apoptosis and tumor suppression. Our recent findings have also demonstrated that the suppression function of caspase-2 context specific. In particular, while deficiency augments lymphoma development EμMyc mouse model, it leads to delayed neuroblastoma Th-MYCN mice. However, unclear how mediates these differential outcomes. Here we utilized RNA sequencing define transcriptomic changes caused by ( Casp2 −/− ) tumors from...