Project description:The cTnT-DK210 DCM mice showed ABRA protein deficiency, sarcomeric disruption, and compromised heart contractility. Heart-specific expression of ABRA in cTnT-DK210 mice restored sarcomeric structures, reversed the disease progress, and rescued the DCM phenotypes. ABRA deficiency and compromised downstream serum response factor-regulated muscle gene expression play a key role in familial DCM caused by the cTnT-DK210 mutation. ABRA is a good therapeutic gene for cTnT-DK210-induced DCM and could be translated to other cTnT mutations-induced familial DCM.
Project description:We used a novel approach to study the acute effect of two frequencies of stimulation (20 Hz and 5 Hz; high and low force, respectively) on gene regulation in people with chronic paralysis. Three hours after the completion of the electrical stimulation protocol (5 Hz or 20 Hz), we sampled the vastus lateralis muscle and examined genes involved with metabolic transcription, glycolysis, oxidative phosphorylation, and mitochondria remodelling. We discovered that the 5 Hz stimulation, despite generating a lower overall force, induced a 5-6 fold increase (p<0.05) in key metabolic transcription factors including PGC-1α, NR4A3, and ABRA. Neither protocol showed a robust regulation of genes for glycolysis, oxidative phosphorylation, and mitochondria remodelling.
Project description:We used a novel approach to study the acute effect of two frequencies of stimulation (20 Hz and 5 Hz; high and low force, respectively) on gene regulation in people with chronic paralysis. Three hours after the completion of the electrical stimulation protocol (5 Hz or 20 Hz), we sampled the vastus lateralis muscle and examined genes involved with metabolic transcription, glycolysis, oxidative phosphorylation, and mitochondria remodelling. We discovered that the 5 Hz stimulation, despite generating a lower overall force, induced a 5-6 fold increase (p<0.05) in key metabolic transcription factors including PGC-1?, NR4A3, and ABRA. Neither protocol showed a robust regulation of genes for glycolysis, oxidative phosphorylation, and mitochondria remodelling. We analyzed skeletal muscle using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Partek Genomic Suites.
Project description:We investigated the short and long term effects of electrically induced exercise on mRNA expression of human paralyzed muscle. We developed an exercise dose that activated the muscle for 0.6% of the day. The short term effects were assessed 3 hours after a single dose of exercise, while the long term effects were assessed after training 5 days per week for at least one year (adherence 81%). A single dose of electrical stimulation increased the mRNA expression of transcriptional, translational, and enzyme regulators of metabolism important to shift muscle toward an oxidative phenotype (PGC-1a, NR4A3, IFRD1, ABRA, PDK4). However, chronic training increased the mRNA expression of specific metabolic pathway genes (BRP44, BRP44L, SDHB, ACADVL), mitochondrial fission and fusion genes (MFF, MFN1, MFN2), and slow muscle fiber genes (MYH6, MYH7, MYL3, MYL2).Furthermore, regulating these same pathways may be critical to developing efficient activity protocols to reduce the prevalence of diabetes in people with longstanding paralysis from SCI. We analyzed skeletal muscle using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Partek Genomic Suites.