Apolipoprotein C-III also known as apo-CIII, and apolipoprotein C3, is a protein that in humans is encoded by the APOC3gene. Apo-CIII is secreted by the liver as well as the small intestine, and is found on triglyceride-rich lipoproteins such as chylomicrons, very low density lipoprotein (VLDL), and remnant cholesterol.[5]
ApoC-III is a relatively small protein containing 79 amino acids that can be glycosylated at threonine-74.[6] The most abundant glycoforms are characterized by an O-linked disaccharide galactose linked to N-acetylgalactosamine (Gal–GalNAc), further modified with up to two sialic acid residues. Less abundant glycoforms are characterized by more complex and fucosylatedglycan moieties.[7]
APOC3 inhibits lipoprotein lipase and hepatic lipase; it is thought to inhibit hepatic uptake[8] of triglyceride-rich particles. The APOA1, APOC3 and APOA4 genes are closely linked in both rat and human genomes. The A-I and A-IV genes are transcribed from the same strand, while the A-1 and C-III genes are convergently transcribed. An increase in apoC-III levels induces the development of hypertriglyceridemia.
Recent evidences suggest an intracellular role for Apo-CIII in promoting the assembly and secretion of triglyceride-rich VLDL particles from hepatic cells under lipid-rich conditions.[9] However, two naturally occurring point mutations in human apoC3 coding sequence, namely Ala23Thr and Lys58Glu have been shown to abolish the intracellular assembly and secretion of triglyceride-rich VLDL particles from hepatic cells.[10][11]
Apo-CIII delays the catabolism of triglyceride rich particles. HDL cholesterol particles that bear Apo-CIII are associated with increased, rather than decreased, risk for coronary heart disease.[15]
Antisense oligonucleotides that bind APOC3 mRNA and prevent its translation have been found to reduce episodes of acute pancreatitis in people with familial chylomicronemia syndrome and lower their triglyceride levels in blood. Adverse effects include thrombocytopenia, which may be prevented by targeting hepatocellularAPOC3 expression with a chemically modified oligonucleotide.[21]
Apolipoprotein CIII is also found on HDL particles. Formation of APOCIII-containing HDL is not a matter of simple binding of APOCII to pre-existing HDL particles but requires the lipid transported ABCA1 in a fashion similar to APOA1-containing HDL.[22] Accumulation of APOCIII on HDL is important for the maintenance of plasma triglyceride homeostasis since it prevents excessive amount of APOCIII on VLDL and other triglyceride rich lipoproteins, thus preventing APOCIII-mediated inhibition of LpL and the subsequent hydrolysis of plasma triglycerides. This may explain the hypertriglyceridemia associated with ABCA1-deficiency in patients with Tangier's disease.
^Vaith P, Assmann G, Uhlenbruck G (Jun 1978). "Characterization of the oligosaccharide side chain of apolipoprotein C-III from human plasma very low density lipoproteins". Biochimica et Biophysica Acta (BBA) - General Subjects. 541 (2): 234–40. doi:10.1016/0304-4165(78)90396-3. PMID208636.
^Nicolardi S, van der Burgt YE, Dragan I, Hensbergen PJ, Deelder AM (May 2013). "Identification of new apolipoprotein-CIII glycoforms with ultrahigh resolution MALDI-FTICR mass spectrometry of human sera". Journal of Proteome Research. 12 (5): 2260–68. doi:10.1021/pr400136p. PMID23527852. S2CID19296928.
^Singh P, Singh M, Kaur TP, Grewal SS (Nov 2008). "A novel haplotype in ApoAI-CIII-AIV gene region is detrimental to Northwest Indians with coronary heart disease". International Journal of Cardiology. 130 (3): e93–5. doi:10.1016/j.ijcard.2007.07.029. PMID17825930.
^Singh P, Singh M, Gaur S, Kaur T (Jun 2007). "The ApoAI-CIII-AIV gene cluster and its relation to lipid levels in type 2 diabetes mellitus and coronary heart disease: determination of a novel susceptible haplotype". Diabetes & Vascular Disease Research. 4 (2): 124–29. doi:10.3132/dvdr.2007.030. PMID17654446. S2CID23793589.
^Richart C, August T, Terra X (2010). "Correspondence: Apolipoprotein C3 Gene Variants in Nonalcoholic Fatty Liver Disease". New England Journal of Medicine. 363 (2): 193–195. doi:10.1056/NEJMc1005265. PMID20647217.
^Peter A, Kantartzis K, Machicao F, Machann J, Wagner S, Templin S, Königsrainer I, Königsrainer A, Schick F, Fritsche A, Häring HU, Stefan N (2012). "Visceral obesity modulates the impact of apolipoprotein C3 Gene variants on liver fat content". International Journal of Obesity. 36 (6): 774–782. doi:10.1038/ijo.2011.154. PMID21829161. S2CID205154071.
^Stroes ES, Alexander VJ, Karwatowska-Prokopczuk E, Hegele RA, Arca M, Ballantyne CM, Soran H, Prohaska TA, Xia S, Ginsberg HN, Witztum JL, Tsimikas S, et al. (Balance Investigators) (2024). "Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome". New England Journal of Medicine. 390 (19): 1781–1792. doi:10.1056/NEJMoa2400201. PMID38587247.
^Kypreos KE (2008). "ABCA1 Promotes the de Novo Biogenesis of Apolipoprotein CIII-Containing HDL Particles in Vivo and Modulates the Severity of Apolipoprotein CIII-Induced Hypertriglyceridemia". Biochemistry. 47 (39): 10491–10502. doi:10.1021/bi801249c. PMID18767813.
Zannis VI, Cole FS, Jackson CL, Kurnit DM, Karathanasis SK (Jul 1985). "Distribution of apolipoprotein A-I, C-II, C-III, and E mRNA in fetal human tissues. Time-dependent induction of apolipoprotein E mRNA by cultures of human monocyte-macrophages". Biochemistry. 24 (16): 4450–55. doi:10.1021/bi00337a028. PMID3931677.
Shelley CS, Sharpe CR, Baralle FE, Shoulders CC (Nov 1985). "Comparison of the human apolipoprotein genes. Apo AII presents a unique functional intron-exon junction". Journal of Molecular Biology. 186 (1): 43–51. doi:10.1016/0022-2836(85)90255-4. PMID3935800.
Hospattankar AV, Brewer HB, Ronan R, Fairwell T (Mar 1986). "Amino acid sequence of human plasma apolipoprotein C-III from normolipidemic subjects". FEBS Letters. 197 (1–2): 67–73. doi:10.1016/0014-5793(86)80300-3. PMID3949020. S2CID83923614.
Law SW, Gray G, Brewer HB (Apr 1983). "cDNA cloning of human apoA-I: amino acid sequence of preproapoA-I". Biochemical and Biophysical Research Communications. 112 (1): 257–64. doi:10.1016/0006-291X(83)91824-7. PMID6404278.
Protter AA, Levy-Wilson B, Miller J, Bencen G, White T, Seilhamer JJ (Dec 1984). "Isolation and sequence analysis of the human apolipoprotein CIII gene and the intergenic region between the apo AI and apo CIII genes". DNA. 3 (6): 449–56. doi:10.1089/dna.1.1984.3.449. PMID6439535.
Levy-Wilson B, Appleby V, Protter A, Auperin D, Seilhamer JJ (Oct 1984). "Isolation and DNA sequence of full-length cDNA for human preapolipoprotein CIII". DNA. 3 (5): 359–64. doi:10.1089/dna.1984.3.359. PMID6548954.
Wu JH, Kao JT, Wen MS, Lo SK (May 2000). "DNA polymorphisms at the apolipoprotein A1-CIII loci in Taiwanese: correlation of plasma APOCIII with triglyceride level and body mass index". Journal of the Formosan Medical Association = Taiwan Yi Zhi. 99 (5): 367–74. PMID10870325.
Inoue Y, Miyazaki M, Tsuji T, Sakaguchi M, Fukaya K, Huh NH, Namba M (Nov 2001). "Reactivation of liver-specific gene expression in an immortalized human hepatocyte cell line by introduction of the human HNF4alpha2 gene". International Journal of Molecular Medicine. 8 (5): 481–87. doi:10.3892/ijmm.8.5.481. PMID11605014.
Well, that’s interesting to know that Psilotum nudum are known as whisk ferns. Psilotum nudum is the commoner species of the two. While the P. flaccidum is a rare species and is found in the tropical islands. Both the species are usually epiphytic in habit and grow upon tree ferns. These species may also be terrestrial and grow in humus or in the crevices of the rocks.
View the detailed Guide of Psilotum nudum: Detailed Study Of Psilotum Nudum (Whisk Fern), Classification, Anatomy, Reproduction
Well, that’s interesting to know that Psilotum nudum are known as whisk ferns. Psilotum nudum is the commoner species of the two. While the P. flaccidum is a rare species and is found in the tropical islands. Both the species are usually epiphytic in habit and grow upon tree ferns. These species may also be terrestrial and grow in humus or in the crevices of the rocks.
View the detailed Guide of Psilotum nudum: Detailed Study Of Psilotum Nudum (Whisk Fern), Classification, Anatomy, Reproduction