![Troponin_Ribbon_Diagram](https://upload.wikimedia.org/wikipedia/commons/3/3f/Troponin_Ribbon_Diagram.png)
Troponin I is a cardiac and skeletal muscle
protein family
A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be c ...
. It is a part of the
troponin
image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL
Troponin, ...
protein complex, where it binds to
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
in thin
myofilament
Myofilaments are the three protein filaments of myofibrils in muscle cells. The main proteins involved are myosin, actin, and titin. Myosin and actin are the ''contractile proteins'' and titin is an elastic protein. The myofilaments act togethe ...
s to hold the actin-tropomyosin complex in place. Troponin I prevents
myosin
Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility.
The first myosin ...
from binding to actin in relaxed muscle. When calcium binds to the troponin C, it causes conformational changes which lead to dislocation of troponin I. Afterwards, tropomyosin leaves the binding site for myosin on actin leading to contraction of muscle. The letter ''I'' is given due to its inhibitory character. It is a useful marker in the laboratory diagnosis of heart attack. It occurs in different plasma concentration but the same circumstances as troponin T - either test can be performed for confirmation of cardiac muscle damage and laboratories usually offer one test or the other.
Three
paralogs
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...
with unique tissue-specific expression patterns are expressed in humans, listed below with their locations and
OMIM
Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM r ...
accessions:
* Slow-twitch skeletal muscle isoform troponin I,
TNNI1
Troponin I, slow skeletal muscle is a protein that in humans is encoded by the ''TNNI1'' gene. It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex
image:Troponin Ribbon Diagram.png, 400px, Ribbon represe ...
(1q31.3, )
* Fast-twitch skeletal muscle isoform troponin I,
TNNI2 (11p15.5, )
* Cardiac troponin I,
TNNI3
Troponin I, cardiac muscle is a protein that in humans is encoded by the ''TNNI3'' gene.
It is a tissue-specific subtype of troponin I
Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, wh ...
(19q13.4, )
cTnI
Cardiac troponin I, often denoted as cTnI, is presented in cardiac muscle tissue by a single isoform with a molecular weight of 23.9 kDa. It consists of 209 amino acid residues. The theoretical pI of cTnI is 9.05.
cTnI differs from other troponins due to its N-terminal extension of 26 amino acids. This extension contains two serines, residues 23 and 24, which are phosphorylated by
protein kinase A
In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulatio ...
in response to beta-adrenergic stimulation and important in increasing the inotropic response. Phosphorylation of cTnI changes the conformation of the protein and modifies its interaction with other troponins as well as the interaction with anti-TnI antibodies. These changes alter the myofilament response to calcium, and are of interest in targeting heart failure. Multiple reaction monitoring of human cTnI has revealed that there are 14 phosphorylation sites and the pattern of phosphorylation observed these sites is changed in response to disease. cTnI has been shown to be phosphorylated by protein kinase A,
protein kinase C,
protein kinase G
cGMP-dependent protein kinase or protein kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle ...
, and
p21-activated kinase 3.
A significant part of cTnI released into the patient's blood stream is phosphorylated. For more than 15 years cTnI has been known as a reliable marker of cardiac muscle tissue injury. It is considered to be more sensitive and significantly more specific in the diagnosis of myocardial infarction than the "golden
marker" of the last decades –
CK-MB
The CPK-MB test (creatine phosphokinase-MB), also known as CK-MB test, is a cardiac marker used to assist diagnoses of an acute myocardial infarction, myocardial ischemia, or myocarditis. It measures the blood level of CK-MB (creatine kinase myoca ...
, as well as total
creatine kinase
Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme () expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create pho ...
,
myoglobin and
lactate dehydrogenase
Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from on ...
isoenzyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...
s.
Troponin I is not entirely specific for myocardial damage secondary to infarction. Other causes of raised troponin I include
chronic kidney failure
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...
,
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
,
subarachnoid haemorrhage
Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of cons ...
and
pulmonary embolus
Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathin ...
.
In veterinary medicine, increased cTnI has been noted from myocardial damage after ionophore toxicity in cattle.
High-sensitivity troponin I testing
The high sensitive troponin I test is a chemiluminescence microparticle immunoassay, which is used to quantitatively determine cardiac troponin I in human plasma and serum. The test can be used to aid in diagnosing myocardial infarction, as a prognostic marker in patients with acute coronary syndrome and to identify the risk (''low, moderate and elevated'') of future cardiovascular diseases such as myocardial infarction, heart failure, ischaemic stroke, coronary revascularisation, and cardiovascular death in asymptomatic people.
High sensitive troponin I has been proven to have superior clinical performance versus high sensitivity troponin T in patients with renal impairment and skeletal muscle disease. It is also not affected by diurnal rhythm, which is important when the test is used as a screening tool for CVD.
Prognostic use
The basis for the modern prevention of CVD lies in the prognosis of the risk of the development of myocardial infarction, stroke or heart failure in the future. Currently, most prognostic models of cardiovascular risk (European SCORE scale, Framingham scale, etc.) are based on the evaluation of traditional risk factors of CVD. This stratification system is indirect and has several limitations, which include the inaccurate forecasting of risks.
These risk scales are heavily dependent on the age of the person. Research data bears evidence that the high sensitive troponin I test enables higher precision in determining the cardiovascular risk group of the individual, if used together with the results of clinical and diagnostic examinations.
- High sensitive troponin I test can help to proactively identify individuals at high cardiovascular risk long before symptoms appear.
The higher the troponin I level in asymptomatic individuals, the higher the likelihood if subclinical myocardial injury.
- It provides greater accuracy in identifying persons at low CVD risk.
- Troponin I is a biomarker that responds to treatment interventions. Reductions in troponin I levels proved to reduce the risk of future CVD.
- High sensitive troponin I used as a screening tool to assess a persons cardiovascular risk and has the potential to reduce the growing cost burden of the healthcare system.
The efficiency of the new test has been confirmed by data collected by international studies with the participation of more than 100,000 subjects.
The ability of high sensitive troponin I to identify individual’s cardiovascular risk in asymptomatic people enables physicians to use it in outpatient/ambulatory practice during preventive check-ups, complex health examinations, or examinations of patients with known risk factors. Knowing which cardiovascular risk group a person belongs to allows physicians to promptly determine patient care tactics well before the development of symptoms, and to prevent adverse outcomes.
Indications for testing
High sensitive troponin I test is recommended for asymptomatic women and men to assess and stratify their cardiovascular risk.
Individuals may or may not have known established cardio-vascular risk factors:
# high blood pressure;
# obesity;
# congenital factors, history of cardiovascular diseases;
# pre-diabetes, diabetes;
# sedentary lifestyle;
# metabolic syndrome;
# dislipidaemia;
# smoking.
Incorporating the high sensitive troponin I test into initial screening will improve the prediction of future CV events and help individuals be more compliant with lifestyle changes and possible medication recommended by their physician.
This might be a step forward for personalized preventive medicine, being especially relevant at an individual level, when clinicians need to weigh the importance of each risk factor and determine if the person needs therapy in addition to lifestyle advice.
The precise frequency of examinations is not pre-determined; it depends on the specific case, risk category and individual characteristics of a patient. The test may be added to the check-up programs or used as a stand along in conjunction with other clinical and diagnostic findings.
History
Troponin was discovered in 1965. It was initially named heart myofibrillar apparatus protein component but was later renamed troponin. In 1971, Grieser and Gergely proved that troponin complex consists of three components, which, considering their specific properties, were named TnC, TnI and TnT. Over the following ten years, several groups of researchers started to demonstrate interest in the research of troponin, and the awareness of these proteins increased rapidly. When, finally, the amino acid sequences of troponin isoforms were determined, the opportunity to research functionally significant regions appeared.
See also
*
Troponin
image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL
Troponin, ...
*
Troponin T
Troponin T (shortened TnT or TropT) is a part of the troponin complex, which are proteins integral to the contraction of skeletal and heart muscles. They are expressed in skeletal and cardiac myocytes. Troponin T binds to tropomyosin and help ...
*
Troponin C
Troponin C is a protein which is part of the troponin complex. It contains four calcium-binding EF hands, although different isoforms may have fewer than four functional calcium-binding subdomains. It is a component of thin filaments, along wi ...
*
Sliding filament model
Sliding may refer to:
*Sliding (dance), also floating or gliding, a group of footwork-oriented dance techniques
*Slide (baseball), an attempt by a baseball runner to avoid getting tagged out
*Sliding (motion)
See also
*Slide (disambiguation)
*Sli ...
References
External links
*
{{Cytoskeletal Proteins
Troponin