Serum amyloid A (SAA) proteins are a family of
apolipoproteinApolipoproteins are proteins that bind to fats . They form lipoproteins, which transport dietary fats through the bloodstream. Dietary fats are digested in the intestine and carried to the liver. Fats are also synthesized in the liver itself. Fats are stored in fat cells...
s associated with high-density lipoprotein (HDL) in plasma. Different isoforms of SAA are expressed constitutively (constitutive SAAs) at different levels or in response to inflammatory stimuli (acute phase SAAs). These proteins are produced predominantly by the liver. The conservation of these proteins throughout invertebrates and vertebrates suggests that SAAs play a highly essential role in all animals.
Acute-phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of
inflammationInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
.
Serum amyloid A (SAA) proteins are a family of
apolipoproteinApolipoproteins are proteins that bind to fats . They form lipoproteins, which transport dietary fats through the bloodstream. Dietary fats are digested in the intestine and carried to the liver. Fats are also synthesized in the liver itself. Fats are stored in fat cells...
s associated with high-density lipoprotein (HDL) in plasma. Different isoforms of SAA are expressed constitutively (constitutive SAAs) at different levels or in response to inflammatory stimuli (acute phase SAAs). These proteins are produced predominantly by the liver. The conservation of these proteins throughout invertebrates and vertebrates suggests that SAAs play a highly essential role in all animals.
Acute-phase serum amyloid A proteins
Acute-phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of
inflammationInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
. These proteins have several roles, including the transport of
cholesterolCholesterol is a lipidic, waxy steroid found in the cell membranes and transported in the blood plasma of all animals. It is an essential component of mammalian cell membranes, where it is required to establish proper membrane permeability and fluidity...
to the
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
for secretion into the
bileBile or gall is a bitter yellowish, blue and green fluid secreted by hepatocytes from the liver of most vertebrates. In many species, bile is stored in the gallbladder between meals and upon eating is discharged into the duodenum where the bile aids the process of digestion of lipids by...
, the recruitment of immune cells to inflammatory sites, and the induction of
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
s that degrade
extracellular matrixIn biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
. A-SAAs are implicated in several chronic inflammatory diseases, such as
amyloidosisIn medicine, amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. A protein is described as being amyloid if, due to an alteration in its secondary structure, it takes on a particular aggregated insoluble form similar to the...
,
atherosclerosisAtherosclerosis is the condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol...
, and
rheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks the joints producing an inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints...
. Three acute-phase SAA isoforms have been reported in mice, called
SAA1Serum amyloid A protein is a protein that in humans is encoded by the SAA1 gene.-Further reading:...
, SAA2, and SAA3. During
inflammationInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
, SAA1 and SAA2 are expressed and induced principally in the
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, whereas SAA3 is induced in many distinct tissues. SAA1 and SAA2 genes are regulated in liver cells by the proinflammatory
cytokineCytokines are any of a number of substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication. They are proteins,...
s
IL-1IL-1 may refer to:* Interleukin 1, a protein* Illinois' 1st congressional district* Illinois Route 1* Building 1 of Infinite Loop , the Headquarters of Apple Inc....
, IL-6, and TNF-α. Both SAA1 and SAA2 are induced up to a 1000-fold in mice under acute inflammatory conditions following exposure to bacterial
lipopolysaccharideLipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is a major...
(LPS). Three A-SAA genes have also been identified in humans, although the third
geneA gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring...
,
SAA3, is believed to represent a
pseudogenePseudogenes are defunct relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell. Although some do not have introns or promoters , most have some gene-like features ,...
that does not generate
messenger RNAMessenger ribonucleic acid is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino...
or
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
.
Constitutive serum amyloid A proteins
A fourth SAA (SAA4) was identified in humans and is expressed constitutively in the liver and, thus, is defined as a constitutive SAA (C-SAA). A similar protein that is now also called SAA4 has since been identified in the mouse; it had originally been designated SAA5.