Molecular Exercise Physiology

Glossary

Henning Wackerhage

University of Aberdeen; [email protected]

Please e-mail me ([email protected]) with corrections or additions.

4E-BP1

Eukaryotic translation initiation factor 4E-binding protein 1; involved in the regulation of protein synthesis

ACE I/D

Polymorphism in the angiotensin-converting enzyme with either an insertion or deletion of a DNA sequence

Acetylation

Addition of an acetyl (CH3CO ) group to a protein, usually on a lysine. Histone aceytlation is a key event in gene regulation

Acquired (adaptive) immune system

The acquired (adaptive) immune system fights against microbes that may have evaded the innate system

Acrylamide gel

Used for gel electrophoresis of proteins especially during Western blots. Acrylamide is toxic and carcinogenic

Action potential

A rapid rise and fall of the membrane potential; occurs in neurons and in muscle fibres and leads to neurotransmitter release and muscle contraction

ACTN3 R577X

Polymorphism in the ACTN3 gene; R stands for arginine and X for a stop codon. If a stop codon is encoded then no functional ACTN3 is produced

Adipokines

Cell-to-cell signalling proteins that are secreted by adipose tissue (fat)

Agarose gel

Used for gel electrophoresis of DNA

PKB (Akt)

Protein kinase B (also known as Akt); a serine/threonine kinase that regulates glucose uptake and protein synthesis via mTOR

Allele

One form or variant of a gene

AMPK

AMP-activated kinase; a serine/threonine kinase involved in the regulation of the adaptation to endurance exercise

Anabolic resistance

A decreased response especially of skeletal muscle to anabolic stimuli such as resistance exercise, hormones or nutrients; contributes to sarcopenia

Angiogenesis

Formation of new blood vessels from existing blood vessels; an adaptation to endurance exercise

Antibody

A protein also known as immunoglobulin produced by B cells. Antibodies bind specifically binds to target proteins; also used as a method to visualize specific proteins for example during immunohistochemistry and Western blotting

Apoptosis

Programmed cell death

Association study

A study where subjects are genotyped for one genotype and this is then compared to the trait investigated

ATPase stain

A histochemical method to stain different types of muscle fibres; usually involves a alkaline or acid preincubation step to only stain one type of muscle fibre

Autophagy

Breakdown of cells to ensure cellular survival during starvation

Autosome

A chromosome that is not a sex chromosome (i.e. not X or Y). There are 22 pairs of autosomes in the human genome

Axon

A projection that usually conveys action potential away from the neuron cell body

B cell

B cells are immune cells produced by the bone marrow

b-cell dysfunction

A state where b-cells of the pancreas release less insulin at a given blood glucose concentration

Bergström needle

A needle used especially for skeletal muscle biopsies

Bioinformatics

Retrieval and analysis of biological data using mathematics and computer science

C/EBPb

A transcription factor believed to be involved in the genesis of the athlete’s heart

C2C12

A mouse muscle myoblast cell line that can be differentiated into myotubes

Calcineurin

A protein phosphatase that dephosphorylates the transcription factor NFAT

Caloric restriction

A reduction of nutrient intake without causing malnutrition; increases lifespan in several species

CaMK

Ca2+/calmodulin-dependent protein kinase; a serine/threonine kinase; involved in the adaptation to endurance exercise

Case–control study

A study where genotype frequencies in subjects with and without a trait are compared

Catalase

An antioxidant enzyme that catalyses the break up of hydrogen peroxide to water and oxygen

cDNA

Complementary DNA; in a reverse transcription reaction, a mRNA template is transcribed into cDNA

Cell line

Cell culture originating from a single cell

Central pattern generator

A neural network that generates rhythmic patterns for movements such as walking or running

Chromatin remodelling

The process of opening up or closing the packaged chromatin, for example by histone modification; a key step in the regulation of gene transcription

Chromosome

Chromosomes are made of DNA tightly coiled DNA

Cyclosporin A

Calcineurin inhibitor

Cytokine

Proteins secreted by leukocytes and other immune cells

Dendrite

Projections of neurons that receive inputs from synapses of other neurons and convey this information to the cell body of the neuron

Dendritic spines

Small protrusions from dendrites that receive input from a single synapse. They are believed to change during learning processes

Diabetes mellitus (types 1 and 2)

A metabolic disease characterized by high blood glucose (hyperglycaemia). In type 1 diabetes, insulin is not produced due to b-cell loss; type 2 diabetes results from insulin resistance and b-cell dysfunction

Diploid

Two copies of each chromosome per cell

DNA

Deoxyribonucleic acid made from guanine, adenine, thymine and cytosine (bases) with a backbone of a deoxyribose sugar connected by phosphate groups

Encode project

Large-scale project to systematically find functional elements in the human genome

Endorphin

Endogenous peptides (opoids) believed to be involved in the ‘runner’s high’

Enhancer

In contrast to (proximal) promoters, enhancers are distal regulatory stretches of DNA to which transcription factors bind. They can be far away from the regulated gene and interact by looping

Epigenetics

Heritable changes in gene expression that are not due to changes in DNA sequence. A loser definition is that epigenetics is genetic control without the need that this is heritable

Epitope

Part of an antigen (antibody-detected protein/molecule) that is recognized by antibodies and other immune system cells

EpoR

Erythropoietin receptor; an activating mutation in this receptor increases the haematocrit in heterozygous carriers

Ethidium bromide

DNA-binding agent that will fluoresce in ultraviolet light. It is a mutagen, carcinogen and teratogen

Excitatory postsynaptic potentials (EPSP) and inhibitory postsynaptic potential ( IPSP)

An excitatory or inhibitory postsynaptic membrane potential change

Exon

DNA sequence in a gene that is present in the final mRNA after introns have been removed

Gene doping

Genetic modification with the aim of enhancing performance

Genetic fingerprinting

Also known as DNA profiling. A technique used to identify individuals via their DNA profiles

Genome–lifestyle divergence hypothesis

A hypothesis postulating a difference between the lifestyle we live and the genome humans have been selected for

Genome-wide association studies (GWAS)

Usually a case–control study where individuals are genotyped with SNP arrays to analyse millions of SNPs (one-base DNA sequence variations)

Gluconeogenesis

Generation of glucose from substrates such as pyruvate, lactate, glycerol, amino acids or fatty acids

Glucokinase

Phosphorylates glucose to glucose-6-phosphate

GLUT4

Glucose transporter type 4; responsive to insulin and exercise. Other glucose transporters exist

Glutathione peroxidase (GPx)

Antioxidant enzymes that reduce lipid hydroperoxides

Glycogenolysis

Breakdown of glycogen to glucose-1-phosphate

Granulocyte

White blood cells marked by granules in their cytoplasm

Haematoxylin & Eosin

A stain which stains nuclei dark purple and protein pink

Hayflick limit

Describes the number of times a human cell can divide until cell division stops; a mechanism linked to ageing

Henneman size principle

States that motor units are recruited from smallest (S) via intermediate (FR) to fastest (FF). Also known as ramp-like recruitment

Heritability

Proportion of the variation of a trait that is due to DNA sequence variations (genetic factors)

Heritage Family Study

Most important study into the genetics of endurance training, led by Prof. Claude Bouchard

Heterozygous

Difference in two alleles (forms or variants of a gene)

Hif-1

Hypoxia-inducible factor 1; transcription factor that is stabilized in response to hypoxia. Regulates the expression of erythropoietin (Epo) and angiogenesis

Histone

Proteins found in cell nuclei that package DNA into nucleosomes; histones are modified to package or unpackage DNA

Hominins

Members of the human tribe; hominin evolution is believed to have started 7 million years ago to the east of the East African rift

Homozygous

Identical alleles (forms or variants of a gene)

Hyperplasia

An increase of cell number

Hypertrophy

An increase of cell size

Hypertrophic cardiomyopathy

A pathological form of cardiac hypertrophy

Hypothalamus

Part of the nervous system that connects to the endocrine system

IGF-1

Insulin-like growth factor 1; increases protein synthesis and causes hypertrophy via the mTOR pathway

IKK

IkB kinase is upstream of NF-kB proteins and sequesters them in an inactive state in the cytoplasm; it causes atrophy

Innate immune system

First defence system; it defends from infection in a non-specific manner

Insulator

Insulators in the DNA are elements that block the interaction between enhancers and promoters

Insulin resistance

Cells fail to exhibit the normal response to insulin which is glucose uptake and glycogen synthesis

Interleukins

Cytokines that are produced by leukocytes and other cells

Intron

DNA sequence of a gene which is removed by splicing

Kinase

An enzyme that transfers phosphate groups, especially from ATP to other molecules. Protein kinases are key signal transduction molecules

Knockout mouse

A genetically engineered mouse where a gene has been inactivated (knocked out)

Leptin

A hormone that regulates energy intake and expenditure

Leukocyte

White blood cells that defend the body against infectious disease

Linkage analysis

A genetic method that allows researchers to identify the location of a disease-causing gene relative to genetic markers

Lipodystrophic

Conditions where the adipose tissue (fat) is absent or reduced

Liquid nitrogen (N2)

Nitrogen in the liquid state; nitrogen boils at –196°C

LKB1

Liver kinase B1; phosphorylates AMPK at Thr172

Long-term potentiation (LTP)

Long-lasting signal transmission between two neurons in response to a stimulus

Lysosome

Organelles that contain acid hydrolase enzymes that break down waste materials

Macrophage

Immune cells that engulf and digest debris and pathogens

MAPK

Mitogen-activated protein kinase; these serine-threonine kinases are involved in signal transduction

Mechanotransduction

Signal transduction events triggered by mechanical stimuli; resistance exercise is one example where mechanotransduction occurs

Metformin

A drug used to treat type 2 diabetes mellitus; activates AMPK

Methylation

Addition of a methyl group to DNA or protein

DNA microarray

Printed DNA spots on a solid surface. It is used to measure the expression of thousands of genes or to detect thousands of SNPs

miRNA

microRNA; small non-coding RNA; regulates gene expression

Mitochondrial haplogroup

DNA sequence variations in human mitochondrial DNA; can be used to trace ancestry

Mitochondrion

Organelle which is the site of oxidative phosphorylation

Mitochondrial biogenesis

Process by which new mitochondria are formed; an adaptation to endurance exercise

Mitosis

Separation of two sets of chromosomes during cell division

Molecular exercise physiology

Molecular exercise physiology is the study of exercise physiology using molecular biology methods

Monoclonal antibody

Antibodies made by identical immune cells

Monogenic trait

Such traits depend mainly on one DNA sequence variation

Motor unit (S, FR, FF)

A motor neuron and the muscle fibres innervated by it. Motor units can e distinguished into slow (S), fatigue-resistant (FR) and fast-fatiguing (FF)

mRNA

Messenger RNA, produced as a result of transcription or gene expression

MtDNA

Mitochondrial DNA; mitochondria have their own DNA which is roughly 16 000 bases long in humans.

mTOR

Mammalian complex of rapamycin; this kinase is a regulator of protein synthesis. It forms two complexes named mTORC1 and mTORC2

Muscle fibre (I, IIa, IIx, IIb)

Multinucleated, differentiated muscle cell. The classification as I, IIa etc. is based on the predominant myosin heavy chain isoform that is expressed

Muscle fibre grouping

A phenomenon typically observed in old muscle. It is due to a loss of one kind of muscle fibre

Myoblast

A mononucleated muscle cell derived, for example, from satellite cells. Myoblasts differentiate to form myotubes and fully differentiated muscle fibres

Myogenic regulatory factors (Myf5, MyoD, myogenin, Mrf4)

Transcription factors that regulate the determination (a cell entering the muscle lineage) and differentiation which is the process where myoblasts form myotubes and muscle fibres

Myokine

Cytokine secreted by muscle cells

Myosin heavy chain

Main part of skeletal muscle myosin proteins. It consumes ATP to produce work and heat. Type I, IIa, IIx and IIb isoforms exist (type IIb is not expressed in many human muscles)

Myostatin

Secreted, muscle-produced protein that inhibits muscle growth

Myotube

Myotubes are formed from myoblasts during differentiation. Myotubes are immature muscle fibres

Natural killer T cell

A set of immune cells; their inactivation can lead to autoimmunity

Neurogenesis

The event where neurons are generated from neural stem and progenitor cells

Neuron

Key cell of the nervous system; electrically excitable cell that transmits information electrically and through chemical signals (neurotransmitter)

Neurotransmitter

Molecules that transmit signals from neurons to target cells which can be other neurons or cells such as muscle fibres

Neutrophil (granulocyte)

Key white blood cell which is part of the innate immune system

Next-generation sequencing (NGS)

High capacity DNA-sequencing methods

NFAT

Nuclear factor of activated T cells; transcription factor activated by dephosphorylation by calcineurin

NF-kB

Nuclear factor-kappa B; involved in immune system regulation and muscle atrophy

Notch pathway

A pathway where cell–cell signals lead to the cleavage of Notch. The intracellular part then migrates to the nucleus and co-activates a transcription factor and regulates gene expression

Nuclear localisation sequence (NLS)

An amino acid sequence that directs a protein to the nucleus

p53

Protein 53; a protein that detects DNA-damaging signals and then regulates DNA repair, cell cycle arrest, or apotosus. Also termed the ‘guardian of the genome’ as it is a tumour suppressor

p70 S6k

Protein 70 S6 kinase; key part of the mTOR pathway; it regulates protein synthesis

Pax7

A marker and identity regulator of satellite cells; Pax7 knockout mice have few satellite cells

PCR

Polymerase chain reaction; a method to amplify or make more of a small stretch of DNA

PEPCK

Phosphoenolpyruvate carboxykinase; an enzyme involved in gluconeogenesis. PEPCK overexpression in mouse muscle leads to an increase in endurance capacity

Personalized medicine

Tailoring medicine to the individual for example based on genetic testing

PGC-1α

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; a gene that is expressed in response to endurance exercise and that drives mitochondrial biogenesis

Phagocytosis

Engulfment of a particle by a cell; macrophages undergo phagocytosis

Phosphatase

An enzyme that removes a phosphate group

Phosphorylation

The process where a serine, threonine or tyrosine on a protein is phosphorylated (PO4 group). A key regulatory event

Physiological cardiac hypertrophy (athlete’s) heart

Exercise-induced eccentric hypertrophy, especially of the left ventricle

PI3K

Phosphoinositide 3-kinase; a kinase which regulates glucose uptake, glycogen synthesis and protein synthesis

Polyclonal antibody

Antibodies produced by B cells against an antigen; the antibodies vary and are frequently produced by inoculation of a suitable mammal

Polygenic trait

Such traits depend on multiple DNA sequence variation

Polymorphism

A common DNA sequence variation that occurs >1% of the population

Proteomics

The high-throughput analysis of proteins

Primary antibody

Antibody that targets the primary target (usually protein of interest) in a Western blot or immunohistochemistry reaction

Primary cell culture

Culture of cells directly obtained from an organ; such cells generally have a limited lifespan in contrast to cell lines

Primer

A short stretch of DNA that binds to the start or end of a target sequence; a key ingredient for the polymerase chain reaction

Promoter

A region of DNA that initiates the transcription of a gene. Transcription factors bind to the promoter

Quantitative trait locus (QTL)

Stretches of DNA where DNA sequence variation can cause the variation of a trait

Rapamycin

An inhibitor of mTOR

Rare mutation

A DNA sequence variation that is rare (<1% of the population is a carrier)

Restriction enzyme

Enzymes that locate and cleave specific, short DNA sequences

Resveratrol

A compound that activates sirtuins and may extend lifespan and increase mitochondrial biogenesis

Reverse transcription

The transcription of RNA into DNA; retroviruses are capable of this

Ribosome

The organelle that synthesizes peptides and proteins from mRNA. Ribosomes are mainly rRNA but also include some ribosomal proteins

RNA

Ribonucleic acid; single stranded, similar to DNA. Made from guanine, adenine, uracil and cytosine

RNA polymerase

An enzyme that reads DNA and produces a RNA template

RONS

Reactive oxygen and nitrogen species

rRNA

Ribosomal RNA; a building block of ribosomes

RT-PCR

Reverse transcription polymerase chain reaction; a method to detect the expression of a gene

RT-qPCR

Reverse transcription quantitative polymerase chain reaction; a method to quantify the expression of a gene

Sanger DNA sequencing

Classical DNA sequencing method

Sarcomere

The basic contraction unit of a muscle; comprises mainly of myosin and actin

Sarcopenia

The loss of muscle mass and function during normal ageing

Satellite cell

The resident, adult muscle stem cell; capable of extensive self renewal and differentiation

Secondary antibody

An antibody to detect a primary antibody; usually conjugated to a visualisation reaction

Senescence

The phenomenon that cells cease to divide after a certain number of divisions

Single nucleotide polymorphism (SNP)

One base DNA sequence variation

Sirtuin

Ribosyltransferases or deacetylases that are involved in the regulation of adaptation to exercise and ageing

Smad

The names comes from the C. elegens gene name SMA and the Drosophila gene name mothers against decapentaplegic. In muscle, Smads are regulated among other by myostatin

Sport and exercise genetics (kinesiogenomics)

The study of heredity in a sport and exercise context

Stable isotope

Chemical isotopes that are not radioactive

Stem cell

A cell that is capable of extensive self-renewal and differentiation. Stem cells are frequently key for the repair of organs

Supercompensation

A time course that describes the decrease of glycogen during exercise and the recovery and overshoot of glycogen during regeneration and after a meal. Such time course does neither describe nor explain common adaptations to exercise

Superoxide dismutase

An enzyme that catalyses the break down of superoxide (O2−) into oxygen and hydrogen peroxide

Synapse

A structure usually at the end of an axon/neuron that triggers the release of neurotransmitter in response to electrical signals

Synergist ablation

Surgical removal of a synergist muscle. The result is frequently the hypertrophy of the remaining muscle

T cell

Immune cell that plays a key role in cell-mediated immunity. T cells mature in the thymus, hence the ‘T’ in the name

Taq polymerase

Thermus aquaticus DNA polymerase. This enzyme can synthesize a DNA double strand on the basis of a single-strand template and is not degraded by heat as the organism lives in hot wells. Key enzyme for the polymerase chain reaction

Telomerase

A ribonucleoprotein enzyme that elongates telomeres

Telomere

6–8 base pair repeats (TTAGGG in vertebrates) at the end of chromosomes; telomeres shorten during each cell division

Tfam

Mitochondrial transcription factor A; a transcription factor that regulates the transcription of mtDNA

Trainability

The magnitude of adaptation to a given exercise training regime. Individuals with high trainability adapt a lot

Trait

A trait is a variable phenotypic characteristic. Examples are eye colour, maximal oxygen uptake or muscle mass

Transcription

Process by which DNA is copied into RNA

Transgenic mouse

A mouse whose genome has been altered by genetic engineering

Translation

Refers to the process where a peptide or protein is synthesized on the basis of an mRNA template on the basis of the ribosome

TNFα

Tumour necrosis factor α; regulates protein breakdown

Twin studies

A study type used to estimate the heritability of a trait

Ubiquitination

The transfer of a ubiquitin group to a protein. Ubiquitination regulates protein breakdown by the proteasome but can also be a signalling event

VEGF

Vascular endothelial growth factor; a key regulator of angiogenesis for example as an adaptation to exercise

Western blot

A method combining gel electrophoresis and antibody-based detection of specific proteins

X-ray crystallography

A method to determine the structure of a molecule