Sarcoplasmic reticulum

The sarcoplasmic reticulum is an intracellular organelle in heart and skeletal muscle that stores calcium. During excitation-contraction coupling, release of calcium from the sarcoplasmic reticulum is the major source of calcium that initiates muscle contraction.

SERCA

SERCA stands for sarcoplasmic/endoplasmic reticulum calcium ATPase. SERCA is the enzyme primarily involved in the transport of calcium into intracellular sarcoplasmic reticulum and endoplasmic reticulum. The sarcoplasmic reticulum (SR) is an intracellular organelle in heart and skeletal muscle that stores calcium. During excitationcontraction coupling, release of calcium from the SR is the major source of calcium that initiates muscle contraction.

Serine/threonine kinase

Kinases are proteins that phosphorylate other proteins, usually resulting in a modification of that protein's function. Serine/threonine kinases are protein kinases that phosphorylate proteins on serine or threonine amino acids.

Signalling pathways

In all cells, complex signalling pathways exist which mediate cell function. Many of these signalling pathways involve kinases that mediate numerous cellular actions, including the effects of hormones binding to receptors which translate into cellular actions. p38 and c-jun N-terminal mitogen-activated protein kinases and calmodulin dependent kinase (CamKII) are examples of kinases involved in important signalling pathways.

6-phosphofructo-2-kinase (PFK-2)

PFK-2 is an enzyme that converts fructose 6-phosphate to fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate is a potent stimulator of 6-phosphofructo-1-kinase (PFK-1), the rate-limiting enzyme of glycolysis. As a result, increasing fructose 2,6-biphosphate is an important mechanism by which glycolysis is regulated.

6-Phosphofructo-1-kinase

6-phosphofructo-1-kinase (PFK-1) is an enzyme that converts fructose 6-phosphate to fructose 1,6- bisphosphate. PFK-1 is the rate-limiting enzyme of glycolysis. As a result, regulation of PFK-1 is an important mechanism by which glycolysis is regulated.

α-Smooth muscle actinb

α-Smooth muscle actin is a contractile protein involved in the contraction of smooth muscle cells.

SREBP-1c

Sterol regulatory element-binding protein (SREBP)-1c is a key regulator of fatty acid metabolism and plays a pivotal role in the transcriptional regulation of different lipogenic genes mediating lipid synthesis. Emerging evidence suggests that insulin resistance and its associated metabolic dyslipidemia result from perturbations in the expression of SREBP-1c, inducing lipogensis and production of VLDL particles.

Stearoyl-CoA desaturase-1 (SCD1)

Stearoyl-CoA desaturase (SCD)1 catalyzes the ratelimiting reaction of monounsaturated fatty acid synthesis and plays an important role in the development of obesity. SCD1 is suppressed by leptin but induced by insulin. SCD-1 expression is also under the control of SREBP-1c. Studies have shown that inhibition of SCD1 can prevent the development of highfat dietinduced obesity and hepatic steatosis.

Strain measured by MRI

Magnetic resonance imaging is a sophisticated technique that produces high-quality images of the body. Newer MRI techniques allow for high resolution of the heart structure and chamber dimensions. Strain measured by MRI is an approach to investigate heart function and wall tension.

Substance P

Substance P is a tachykinin and physiologically acts as a neurotransmitter and neuromodulator in the nervous system. Pathologically, it can also trigger malignant cells to release cytokines and increase cell proliferation rates.

Subtypes (A1 and A2) of surface membrane P1 receptors

Purinergic receptors (designated “P” receptors) use purine nucleotides as ligands. The P1 class of purinergic receptors use adenosine as a ligand. These P1 receptors can further be classified as A1, A2, and A3 receptors. The vasodilatory effects of adenosine are primarily mediated by binding to A2 receptors. The direct chronotropic effects of adenosine on the heart, and many of its cardioprotective actions are mediated by adenosine binding to A1 receptors. Ischemic preconditioning involves a series of intracellular events that are initiated with the activation of the A1 receptor, and end at the sensitive K+ ATP channels of the mitochondria. New evidence points to a role for adenosine in promoting neovascularization through a mechanism that requires interaction between the adenosine receptor subtype 2A (A(2A)R).

Superoxide

Superoxide is a free radical. It is an oxygen molecule that has an unpaired electron. This molecule can react with lipids, proteins, DNA, and RNA, causing tissue damage.

TC10 family of Rho GTP-binding proteins

The Rho GTPases are related to the Ras proto-oncogenes and consist of 22 family members. These proteins have important roles in regulating the organization of the actin filament system, and thereby the morphogenesis of vertebrate cells as well as their ability to migrate. Signal initiation from the insulin receptor and a series of adapter proteins result in the activation of the G protein TC10. TC10 can influence a number of cellular processes, including changes in the actin cytoskeleton, recruitment of adapter proteins CIP4, and assembly of the exocyst complex. These events play crucial roles in the trafficking, docking and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 at the plasma membrane.

Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)

Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) is an assay used to detect double-strand DNA breaks. This assay is used for in situ identification of apoptotic cells by detecting DNA damage.

Thiazolidinediones (TZDs)

TZDs are a class of drugs that act as ligands for PPARγ. An example of a TZD is rosiglitazone. Activation of PPARγ by TZDs can improve muscle insulin sensitivity. They also can have beneficial effects on blood lipids and vascular smooth muscle lipid accumulation.

Thiobarbituric acid-reacting substances (TBARS)

Thiobarbituric acid-reacting substances (TBARS) is a simple assay that is used to measure malonyldialdehyde, a product of free radical lipid peroxidation.

Thioheptadecanoic acid

Thioheptadecanoic is a 16-carbon fatty acid that can be radiolabeled and used as a tracer for fatty acid uptake into the heart. One of the radiolabels that can attached to heptadecanoic acid is an 18fluoro group resulting in 18-fluoro-thioheptadecanoic acid (FTHA). A gammacamera can then be used to measure FTHA uptake into the heart. This approach is used to assess fatty acid metabolism in the heart.

Thioredoxin peroxidase

Thioredoxin peroxidase is a peroxiredoxin that uses thiols as reductants. Since they use hydrogen peroxide as a substrate, they are an antioxidant enzyme.

Thioredoxin reductase

Thioredoxin reductase is a major cellular protein disulfide reductase. This enzyme has antioxidant activity.

Thrombomodulin

Thrombomodulin is a key component of the anticoagulant protein C pathway and is a major contributor to vascular thromboresistance. It inhibits blood coagulation.

Thromboxane A₂

Thromboxane A₂ is a product of the cycloxygenase pathway of arachidonic acid metabolism. The production of PGH2 from arachidonic acids by cycloxygenase can be used for a number of different eicosanoid products, including the production of prostaglandins. Metabolism of PGH2 by thromboxane synthase, which is abundant in lung and platelets, results in the production of thromboxane A₂. Thromboxane A₂ has a variety of biological effects, including vasoconstriction and promotion of platelet aggregation.

Tissue factor pathway inhibitor

Tissue factor pathway inhibitor is a critical inhibitor that modulates tissue factor-induced coagulation.

Tissue plasminogen activator

Tissue plasminogen activator is a thrombolytic agent that disrupts blood clots. It is widely used to break up thrombus in patients with acute myocardial infarction or strokes.

Tocopheroxyl radical

Tocopheroxyl radicals are formed from a-tocopherol (vitamin E). Vitamin E is an antioxidant, since it is an efficient scavenger of lipid peroxyl radicals. Tocopheroxyl radicals are formed during this process, which can then be recycled back to a-tocopherol.

Transfection

In molecular biology, the term transfection usually refers to the introduction of foreign DNA or RNA into a cell, resulting in the expression of a protein encoded by that DNA or RNA.

Transforming growth factor (TGF)-β

Transforming growth factor (TGF)-β is a growth factor that has an important role in controlling fibroblast growth and accumulation of extracellular matrix proteins. Increases in TGF-β have been implicated in the maladaptive response to cardiac hypertrophy.

Triacylglycerol

Triacylglycerol is the major storage form of fatty acids in the body and consists of three fatty acids attached to a glycerol backbone. Fatty acid storage in adipocytes primarily occurs in the form of triacylglycerol. The heart also contains sizable triacylglycerol stores as a source of fatty acids for energy production.

Troglitazon

Troglitazone is an agonist of PPARγ. It belongs to a class of compounds called thiazolidinediones. Activation of PPARγ ?with troglitazone has potential clinical application in the treatment of insulin resistance and atherosclerosis

Tryptophan-rich sensory protein (TspO)

Tryptophan-rich sensory protein (TspO) is a tryptophan-rich protein that negatively affects the transcriptional expression of several genes.

Tubulin

Tubulin is a protein that forms a hollow cylindrical structure that is important for the cytoskeleton of cells. a- And b-tubulin subunits form a helical array that makes up the cytoskeletal structure.

Tumor necrosis factor (TNF-α)

Tumor necrosis factor (TNF-α) is a cytokine that acts via receptors to mediate a number of biological effects, including the inflammatory response. The role of cytokines in the pathogenesis of systolic heart failure (HF) has been well established. TNF-α can also activate the intrinsic mitochondrial death pathway that is responsible for the cardiac myocyte apoptosis.

Tyrosine kinase

Tyrosine kinase is a kinase that phosphorylates tyrosine residues on proteins. Many different tyrosine kinases exist, an important one being the insulin receptor. Insulin binding to the receptor stimulates a tyrosine kinase to initiate the downstream insulin-signaling pathway.

Ubiquinol-cytochrome c reductase (complex III)

Ubiquinol-cytochrome c reductase is the third complex of the electron transport chain. It is involved in mitochondrial respiration, which is a major source of energy for cells.

Ubiquinone

Ubiquinone (often called coenzyme Q10) is a quinine compound that serves as an electron carrier between flavoproteins. Ubiquinone is a component of the oxidative phosphorylation process in mitochondria that converts the energy from fatty acids and carbohydrates into ATP (the main source of energy used to drive cellular machinery and synthesis). An additional role of ubiquinone is that it acts in its reduced form (ubiquinol) as an antioxidant.

Uncoupling of NO synthase

Nitric oxide (NO*) is an important protective molecule in the vasculature. Endothelial NO* synthase (eNOS) is responsible for most of the vascular NO* produced. The normal function of eNOS is to oxidize its substrate L-arginine to L-citrulline and NO*. This normal function of eNOS requires dimerization of the enzyme in the presence of the substrate L-arginine. This reaction requires an essential co-factor, tetrahydro-L-biopterin (BH4), one of the most potent naturally occurring reducing agents. However, if BH4 is diminished due to oxidation, eNOS can promote the production of the free radical, superoxide (O2*–). If this occurs, the process is referred to as eNOS uncoupling.

Uncoupling protein

Uncoupling proteins (UCP) are proteins that are present in the inner mitochondrial membrane of cells that dissipate the proton gradient across this membrane. As a result of this action, mitochondrial respiration produces heat instead of ATP. Heart and skeletal muscle contain two isoforms of UCPs, UCP2 and UCP3. The exact function of these UCP’s is not clear, but they may be involved in decreasing reactive oxygen species production by the mitochondria or transporting excess fatty acids out of the mitochondria. The expression of UCPs in the mitochondria is increased in muscle exposed to high fats.