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Junctophilin-2 Protects Cardiomyocytes Against Palmitate-Induced Injury, Xiaoyun Ji Dec 2019

Junctophilin-2 Protects Cardiomyocytes Against Palmitate-Induced Injury, Xiaoyun Ji

Electronic Thesis and Dissertation Repository

Cardiac lipotoxicity may induce cardiomyocyte apoptosis, eventually leading to myocardial dysfunction and heart failure. This study investigated whether and how junctophilin-2 (JPH2) plays a role in palmitate-induced apoptosis in cardiomyocytes. Here, we found palmitate incubation reduced JPH2 protein levels, increased cytosolic Ca2+ and induced apoptosis in cardiomyocytes. JPH2 over-expression prevented the increased cytosolic Ca2+ and apoptosis in palmitate-stimulated cardiomyocytes. JPH2 over-expression also attenuated palmitate-induced CCAAT-enhancer-binding protein homologous protein (CHOP) expression and CHOP deletion alleviated palmitate-induced apoptosis. Furthermore, blocking Ca2+ release from ryanodine receptor-2 (RyR2) prevented palmitate-stimulated CHOP induction and apoptosis. Additionally, JPH2 silencing elevated cytosolic Ca2+ …


The Role Of Atf4 In Amyloid-Beta-Induced Neuronal Death., Gillian Petroff Aug 2019

The Role Of Atf4 In Amyloid-Beta-Induced Neuronal Death., Gillian Petroff

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is partially characterized by excessive accumulation of amyloid-b (Ab) in the brain. Ab oligomers have greater toxicity than Ab fibrils and induce neuronal stress. The Integrated Stress Response (ISR) is activated in response to cellular stress and increases expression of activating transcription factor 4 (ATF4) and its target genes. Prolonged activation has been shown to induce aberrant cell death, and increased markers of the ISR have been found in the brains of AD patients. However, the exact mechanism of amyloid-b-induced death is largely unknown. We aimed to determine if Ab-induced neuronal death occurs through ATF4-mediated upregulation of …


Hei-Oc1 Cochlear Cells As An In Vitro Model To Study The Role Of Connexins In Ototoxicity And Hearing Loss, Rianne Beach Aug 2019

Hei-Oc1 Cochlear Cells As An In Vitro Model To Study The Role Of Connexins In Ototoxicity And Hearing Loss, Rianne Beach

Electronic Thesis and Dissertation Repository

Connexin 26 (Cx26) and Cx30 mediate the intercellular exchange of metabolites and ions within the cochlea in a process known as gap junctional intercellular communication (GJIC). Cochlear cell death and subsequent hearing loss can arise after treatment with ototoxic therapeutics and Cx26 mutant expression. We investigated the role of connexins and GJIC in the development of ototoxicity in HEI-OC1 cochlear-derived cells. The susceptibility of HEI-OC1 cells to aminoglycoside antibiotics and cisplatin-induced cell death was not influenced by the ablation of connexins and GJIC. However, the expression of mitochondrial apoptosis or ER stress markers was altered by the degree of GJIC. …


High Molecular-Weight Hyaluronan Prevents Basal Cell Carcinoma Via Promoting Apoptosis In Cancer-Initiating Adult Stem Cells, Violet Liu Apr 2019

High Molecular-Weight Hyaluronan Prevents Basal Cell Carcinoma Via Promoting Apoptosis In Cancer-Initiating Adult Stem Cells, Violet Liu

Electronic Thesis and Dissertation Repository

Basal cell carcinoma (BCC), a keratinocyte cancer, is the most common human neoplasm worldwide. Although rarely metastatic, BCC is associated with high morbidity rates with globally rising incidence rates. Accompanying the increase in newly diagnosed cases, the societal cost for BCC treatment in Canada is also expected to inflate, exceeding over $900 million/year by 2031. Chronic UVB exposure has been identified as the primary carcinogen that causes activating mutations in the hedgehog signaling pathway. However, there are no effective preventative methods against BCC, since meta-analyses report sunscreen application does not reduce BCC in compliant patients. The native high molecular-weight hyaluronan …