Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Indole-3-acetic acid: Difference between pages

| Watchedfields = changed

| verifiedrevid = 476999984

|PIN=(1''H''-Indol-3-yl)acetic acid

|OtherNames=Indole-3-acetic acid,<br/>indolylacetic acid,<br/>1''H''-Indole-3-acetic acid,<br/>indoleacetic acid,<br/>heteroauxin,<br/>IAA

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 6U1S09C61L

| SMILES = O=C(O)Cc1c[nH]c2ccccc12

| C=10|H=9|N=1|O=2

| Appearance=White solid

| MeltingPtC=168 to 170

| Solubility=insoluble in water. Soluble in ethanol to 50mg/ml

| AutoignitionPt=

'''Indole-3-acetic acid''' ('''IAA''', '''3-IAA''') is the most common naturally occurring [[plant hormone]] of the [[auxin]] class. It is the best known of the auxins, and has been the subject of extensive studies by plant physiologists.<ref name="simon">{{cite journal |doi=10.1016/j.plantsci.2010.12.007 |title=Why plants need more than one type of auxin |year=2011 |last1=Simon |first1=Sibu |last2=Petrášek |first2=Jan |journal=Plant Science |volume=180 |issue=3 |pages=454–60 |pmid=21421392|url=https://zenodo.org/record/894396 }}</ref> IAA is a derivative of [[indole]], containing a carboxymethyl substituent. It is a colorless solid that is soluble in polar organic solvents.

== Biosynthesis ==

{{Main|Auxin}}

IAA is predominantly produced in cells of the apex ([[bud]]) and very young leaves of a [[plant]]. Plants can synthesize IAA by several independent biosynthetic pathways. Four of them start from [[tryptophan]], but there is also a biosynthetic pathway independent of tryptophan.<ref name="Zhao 2010">{{cite journal |doi=10.1146/annurev-arplant-042809-112308 |title=Auxin Biosynthesis and Its Role in Plant Development |year=2010 |last1=Zhao |first1=Yunde |journal=Annual Review of Plant Biology |volume=61 |pages=49–64 |pmid=20192736 |pmc=3070418}}</ref> Plants mainly produce IAA from tryptophan through [[indole-3-pyruvic acid]].<ref>{{cite journal |bibcode=2011PNAS..10818512M |title=The main auxin biosynthesis pathway in Arabidopsis |last1=Mashiguchi |first1=Kiyoshi |last2=Tanaka |first2=Keita |last3=Sakai |first3=Tatsuya |last4=Sugawara |first4=Satoko |last5=Kawaide |first5=Hiroshi |last6=Natsume |first6=Masahiro |last7=Hanada |first7=Atsushi |last8=Yaeno |first8=Takashi |last9=Shirasu |first9=Ken |last10=Yao |first10=H. |last11=McSteen |first11=P. |last12=Zhao |first12=Y. |last13=Hayashi |first13=K.-i. |last14=Kamiya |first14=Y. |last15=Kasahara |first15=H. |volume=108 |year=2011 |pages=18512–7 |journal=Proceedings of the National Academy of Sciences |doi=10.1073/pnas.1108434108 |issue=45 |pmid=22025724 |pmc=3215075|display-authors=8 |doi-access=free }}</ref><ref>{{cite journal |bibcode=2011PNAS..10818518W |title=Conversion of tryptophan to indole-3-acetic acid by TRYPTOPHAN AMINOTRANSFERASES OF ARABIDOPSIS and YUCCAs in Arabidopsis |last1=Won |first1=Christina |last2=Shen |first2=Xiangling |last3=Mashiguchi |first3=Kiyoshi |last4=Zheng |first4=Zuyu |last5=Dai |first5=Xinhua |last6=Cheng |first6=Youfa |last7=Kasahara |first7=Hiroyuki |last8=Kamiya |first8=Yuji |last9=Chory |first9=Joanne |last10=Zhao |first10=Y. |volume=108 |year=2011 |pages=18518–23 |journal=Proceedings of the National Academy of Sciences |doi=10.1073/pnas.1108436108 |issue=45 |pmid=22025721 |pmc=3215067|display-authors=8 |doi-access=free }}</ref> IAA is also produced from tryptophan through [[indole-3-acetaldoxime]] in ''[[Arabidopsis thaliana]]''.<ref>{{cite journal |bibcode=2009PNAS..106.5430S |title=Biochemical analyses of indole-3-acetaldoxime-dependent auxin biosynthesis in Arabidopsis |last1=Sugawara |first1=Satoko |last2=Hishiyama |first2=Shojiro |last3=Jikumaru |first3=Yusuke |last4=Hanada |first4=Atsushi |last5=Nishimura |first5=Takeshi |last6=Koshiba |first6=Tomokazu |last7=Zhao |first7=Yunde |last8=Kamiya |first8=Yuji |last9=Kasahara |first9=Hiroyuki |volume=106 |year=2009 |pages=5430–5 |journal=Proceedings of the National Academy of Sciences |doi=10.1073/pnas.0811226106 |issue=13 |pmid=19279202 |jstor=40455212 |pmc=2664063 |doi-access=free }}</ref>

In rats, IAA is a product of both endogenous and colonic microbial metabolism from dietary [[tryptophan]] along with [[tryptophol]]. This was first observed in rats infected by ''[[Trypanosoma brucei gambiense]]''.<ref>{{cite journal |author1=Howard Stibbs Henry |author2=Richard Seed John | year = 1975 | title = Short-Term Metabolism of [14C]Tryptophan in Rats Infected with Trypanosoma brucei gambiense | journal = J Infect Dis | volume = 131 | issue = 4| pages = 459–462 | doi = 10.1093/infdis/131.4.459 | pmid=1117200}}</ref> A 2015 experiment showed that a high-tryptophan diet can decrease serum levels of IAA in mice, but that in humans, protein consumption has no reliably predictable effect on plasma IAA levels.<ref>{{cite journal |vauthors=Poesen R, Mutsaers HA |display-authors=etal | date = Oct 2015 | title = The Influence of Dietary Protein Intake on Mammalian Tryptophan and Phenolic Metabolites | journal = PLOS ONE | volume = 10 | issue = 10| page = e0140820 | doi = 10.1371/journal.pone.0140820| pmid=26469515 | pmc=4607412| bibcode=2015PLoSO..1040820P |doi-access=free }}</ref> Human cells have been known to produce IAA in vitro since the 1950s,<ref>{{Cite journal| issn = 0021-9258| volume = 234| issue = 1| pages = 81–86| last1 = Weissbach| first1 = H.| last2 = King| first2 = W.| last3 = Sjoerdsma| first3 = A.| last4 = Udenfriend| first4 = S.| title = Formation of indole-3-acetic acid and tryptamine in animals: a method for estimation of indole-3-acetic acid in tissues| journal = The Journal of Biological Chemistry| date = January 1959| doi = 10.1016/S0021-9258(18)70339-6| pmid = 13610897| doi-access = free}}</ref> and the critical biosynthesis gene IL4I1 has been identified.<ref>{{Cite journal| doi = 10.1021/acs.jafc.0c03735| issn = 1520-5118| last1 = Zhang| first1 = Xia| last2 = Gan| first2 = Min| last3 = Li| first3 = Jingyun| last4 = Li| first4 = Hui| last5 = Su| first5 = Meicheng| last6 = Tan| first6 = Dongfei| last7 = Wang| first7 = Shaolei| last8 = Jia| first8 = Man| last9 = Zhang| first9 = Liguo| last10 = Chen| first10 = Gang| title = An endogenous indole pyruvate pathway for tryptophan metabolism mediated by IL4I1| journal = Journal of Agricultural and Food Chemistry| date = 2020-08-31| volume = 68| issue = 39| pages = 10678–10684| pmid = 32866000| s2cid = 221402986}}</ref><ref>{{Cite journal| doi = 10.1016/j.cell.2020.07.038| issn = 1097-4172| last1 = Sadik| first1 = Ahmed| last2 = Somarribas Patterson| first2 = Luis F.| last3 = Öztürk| first3 = Selcen| last4 = Mohapatra| first4 = Soumya R.| last5 = Panitz| first5 = Verena| last6 = Secker| first6 = Philipp F.| last7 = Pfänder| first7 = Pauline| last8 = Loth| first8 = Stefanie| last9 = Salem| first9 = Heba| last10 = Prentzell| first10 = Mirja Tamara| last11 = Berdel| first11 = Bianca| last12 = Iskar| first12 = Murat| last13 = Faessler| first13 = Erik| last14 = Reuter| first14 = Friederike| last15 = Kirst| first15 = Isabelle| last16 = Kalter| first16 = Verena| last17 = Foerster| first17 = Kathrin I.| last18 = Jäger| first18 = Evelyn| last19 = Guevara| first19 = Carina Ramallo| last20 = Sobeh| first20 = Mansour| last21 = Hielscher| first21 = Thomas| last22 = Poschet| first22 = Gernot| last23 = Reinhardt| first23 = Annekathrin| last24 = Hassel| first24 = Jessica C.| last25 = Zapatka| first25 = Marc| last26 = Hahn| first26 = Udo| last27 = von Deimling| first27 = Andreas| last28 = Hopf| first28 = Carsten| last29 = Schlichting| first29 = Rita| last30 = Escher| first30 = Beate I.| last31 = Burhenne| first31 = Jürgen| last32 = Haefeli| first32 = Walter E.| last33 = Ishaque| first33 = Naveed| last34 = Böhme| first34 = Alexander| last35 = Schäuble| first35 = Sascha| last36 = Thedieck| first36 = Kathrin| last37 = Trump| first37 = Saskia| last38 = Seiffert| first38 = Martina| last39 = Opitz| first39 = Christiane A.| title = IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression| journal = Cell| date = 2020-08-17| volume = 182| issue = 5| pages = 1252–1270.e34| pmid = 32818467| s2cid = 221179265| doi-access = free}}</ref>

==Biological effects==

As all auxins, IAA has many different effects, such as inducing [[Cell (biology)|cell]] elongation and [[cell division]] with all subsequent results for plant growth and development. On a larger scale, IAA serves as signaling molecule necessary for development of plant organs and coordination of growth.

===Plant gene regulation===

IAA enters the plant cell nucleus and binds to a protein complex composed of a [[ubiquitin-activating enzyme]] (E1), a [[ubiquitin-conjugating enzyme]] (E2), and a [[ubiquitin ligase]] (E3), resulting in [[Ubiquitin#Ubiquitylation|ubiquitination]] of [[Auxin#Aux/IAA, ARF, TIR1, SCF auxin regulatory pathways|Aux/IAA]] proteins with increased speed.<ref>{{cite journal |title=Function and regulation of cullin-RING ubiquitin ligases. |year=2005 |last1=Pekker |first1=MD |last2=Deshaies |first2=RJ |journal=Plant Cell |volume=6 |issue=1 |pages=9–20 |doi=10.1038/nrm1547 |pmid=15688063 |s2cid=24159190 |url=https://authors.library.caltech.edu/55905/2/nrm1547-S1.pdf }}</ref> Aux/IAA proteins bind to [[Auxin#Aux/IAA, ARF, TIR1, SCF auxin regulatory pathways|auxin response factor]] (ARF) proteins, forming a heterodimer, suppressing ARF activity.<ref>{{cite journal |title=Aux/IAA proteins contain a potent transcriptional repression domain. |year=2004 |last1=Tiwari |first1=SB |last2=Hagen |first2=G |last3=Guilfoyle |first3=TJ |journal=Plant Cell |volume=16 |issue=2 |pages=533–43 |doi=10.1105/tpc.017384|pmid=14742873 |pmc=341922 }}</ref> In 1997 it was described how ARFs bind to auxin-response gene elements in promoters of auxin regulated genes, generally activating transcription of that gene when an Aux/IAA protein is not bound.<ref>{{cite journal |title=ARF1, a transcription factor that binds to auxin response elements. |year=1997 |last1=Ulmasov |first1=T |last2=Hagen |first2=G |last3=Guilfoyle |first3=TJ |journal=Science |volume=276 |issue=5320 |pages=1865–68 |doi=10.1126/science.276.5320.1865 |pmid=9188533}}</ref>

IAA inhibits the [[photorespiration|photorespiratory]]-dependent cell death in photorespiratory [[catalase]] mutants. This suggests a role for auxin signalling in stress tolerance.<ref>{{cite journal |vauthors=Kerchev P, Muhlenbock P, Denecker J, Morreel K, Hoeberichts FA, van der Kelen K, Vandorpe M, Nguyen L, Audenaert D, van Breusegem F | date = Feb 2015 | title = Activation of auxin signalling counteracts photorespiratory H2O2-dependent cell death | journal = Plant Cell Environ | volume = 38 | issue = 2| pages = 253–65 | pmid = 26317137 | doi=10.1111/pce.12250| doi-access = free }}</ref>

===Bacterial physiology===

IAA production is widespread among environmental bacteria that inhabit soils, waters, but also plant and animal hosts. Distribution and [[substrate specificity]] of the involved enzymes suggests these pathways play a role beyond plant-microbe interactions.<ref>{{cite journal |vauthors=Patten CL, Blakney AJ, Coulson TJ | date = Nov 2013 | title = Activity, distribution and function of indole-3-acetic acid biosynthetic pathways in bacteria | journal = Crit Rev Microbiol | volume = 39 | issue = 4| pages = 395–415 | doi = 10.3109/1040841X.2012.716819 | pmid = 22978761 | s2cid = 22123626 }}</ref> ''[[Enterobacter cloacae]]'' can produce IAA, from aromatic and branched-chain amino acids.<ref>{{cite journal |vauthors=Parsons CV, Harris DM, Patten CL |display-authors=etal | date = Sep 2015 | title = Regulation of indole-3-acetic acid biosynthesis by branched-chain amino acids in Enterobacter cloacae UW5 | journal = FEMS Microbiol Lett | volume = 362 | issue = 18| pages = fnv153| doi = 10.1093/femsle/fnv153 | pmid = 26347301| doi-access = free }}</ref>

===Fungal symbiosis===

Fungi can form a fungal mantle around roots of perennial plants called [[ectomycorrhiza]]. A fungus specific to [[spruce]] called ''[[Tricholoma vaccinum]]'' was shown to produce IAA from tryptophan and excrete it from its [[hyphae]]. This induced branching in cultures, and enhanced [[Hartig net]] formation. The fungus uses a multidrug and toxic extrusion (MATE) transporter Mte1.<ref>{{cite journal |vauthors=Krause K, Henke C, Asiimwe T, Ulbricht A, Klemmer S, Schachtschabel D, Boland W, Kothe E | date = Oct 2015 | title = Biosynthesis and Secretion of Indole-3-Acetic Acid and Its Morphological Effects on Tricholoma vaccinum-Spruce Ectomycorrhiza | journal = Appl Environ Microbiol | volume = 81 | issue = 20| pages = 7003–11 | doi = 10.1128/AEM.01991-15 | pmid = 26231639 | pmc = 4579454 | bibcode = 2015ApEnM..81.7003K }}</ref> Research into IAA-producing fungi to promote plant growth and protection in sustainable agriculture is underway.<ref>{{cite journal | vauthors = Fu SF, Wei JY, Chen HW, Liu YY, Lu HY, Chou JY | date = Aug 2015 | title = Indole-3-acetic acid: A widespread physiological code in interactions of fungi with other organisms | journal = Plant Signal Behav | volume = 10 | issue = 8| page = e1048052 | doi = 10.1080/15592324.2015.1048052 | pmid = 26179718 | pmc = 4623019 }}</ref>

===Skatole biosynthesis===

[[Skatole]], the odorant in feces, is produced from [[tryptophan]] via indoleacetic acid. [[Decarboxylation]] gives the methylindole.<ref>{{cite journal |last1= Whitehead |first1= T. R. |last2= Price |first2= N. P. |last3= Drake |first3= H. L. |last4= Cotta |first4= M. A. |title= Catabolic pathway for the production of skatole and indoleacetic acid by the acetogen Clostridium drakei, Clostridium scatologenes, and swine manure |journal= Applied and Environmental Microbiology |volume = 74|issue = 6|pages = 1950–3|pmid= 18223109 |pmc = 2268313|date= 25 January 2008 |doi = 10.1128/AEM.02458-07|bibcode= 2008ApEnM..74.1950W }}</ref><ref>{{cite journal|doi=10.1093/ajcn/32.1.173|pmid=367144|title=Microbial metabolites of tryptophan in the intestinal tract with special reference to skatole|journal=The American Journal of Clinical Nutrition|volume=32|issue=1|pages=173–178|year=1979|last1=Yokoyama|first1=M. T.|last2=Carlson|first2=J. R.|doi-access=free}}</ref>

==Synthesis==

Chemically, it can be synthesized by the reaction of [[indole]] with [[glycolic acid]] in the presence of base at 250&nbsp;°C:<ref>{{ OrgSynth | author = Johnson, Herbert E. | author2 = Crosby, Donald G. | title = Indole-3-acetic Acid | volume = 44 | pages = 64 | collvol = 5 | collvolpages = 654 | year = 1964 | prep = CV5P0654 }}</ref>

:[[File:Synthesis of indole-3-acetic acid.png|450px]]

Alternatively the compound has been synthesized by [[Fischer indole synthesis]] using [[glutamic acid]] and [[phenylhydrazine]].<ref>{{cite journal|last1=Fox|first1=Sidney W.|last2=Bullock|first2=Milon W.|title=Synthesis of Indoleacetic Acid from Glutamic Acid and a Proposed Mechanism for the Conversion|journal=Journal of the American Chemical Society|date=1951|volume=73|issue=6|pages=2754–2755|doi=10.1021/ja01150a094}}</ref> Glutamic acid was converted to the necessary [[aldehyde]] via [[Strecker degradation]].

Many methods for its synthesis have been developed since its original synthesis from indole-3-acetonitrile.<ref>{{cite journal |doi=10.1002/cber.19250580917 |title=Synthetische Versuche in der Indol-Gruppe, VI.: Eine neue Synthese von β-Indolyl-alkylaminen |year=1925 |last1=Majima |first1=Rikō |last2=Hoshino |first2=Toshio |journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series) |volume=58 |issue=9 |pages=2042–6}}</ref>

== History and synthetic analogs ==

William Gladstone Tempelman studied substances for growth promotion at [[Imperial Chemical Industries]] Ltd. After 7 years of research he changed the direction of his study to try the same substances at high concentrations in order to stop plant growth. In 1940 he published his finding that IAA killed broadleaf plants within a cereal field.<ref>{{cite journal |author1=Templeman W. G. |author2=Marmoy C. J. | year = 2008 | title = The effect upon the growth of plants of watering with solutions of plant-growth substances and of seed dressings containing these materials | journal = Annals of Applied Biology | volume = 27 | issue = 4| pages = 453–471 | doi = 10.1111/j.1744-7348.1940.tb07517.x }}</ref>

The search for an acid with a longer half life, i.e. a metabolically and environmentally more stable compound led to [[2,4-dichlorophenoxyacetic acid]] (2,4-D) and [[2,4,5-trichlorophenoxyacetic acid]] (2,4,5-T), both [[phenoxy herbicide]]s and analogs of IAA. Robert Pokorny an industrial chemist for the C.B. Dolge Company in [[Westport, Connecticut]] published their synthesis in 1941.<ref>{{cite journal | author = Pokorny Robert | year = 1941 | title = New Compounds. Some Chlorophenoxyacetic Acids | journal = J. Am. Chem. Soc. | volume = 63 | issue = 6| pages = 1768 | doi = 10.1021/ja01851a601 }}</ref> When sprayed on broad-leaf dicot plants, they induce rapid, uncontrolled growth, eventually killing them. First introduced in 1946, these herbicides were in widespread use in [[agriculture]] by the middle of the 1950s.{{citation needed|date=April 2013}}

Other less expensive synthetic [[auxin]] analogs on the market for use in [[horticulture]] are [[indole-3-butyric acid]] (IBA) and [[1-Naphthaleneacetic acid|1-naphthaleneacetic acid]] (NAA).<ref>{{Cite web |title=PGR Planofix - Crop Science India |url=https://www.cropscience.bayer.in/Products-H/Brands/Crop-Protection/PGR-Planofix |access-date=2022-04-28 |website=www.cropscience.bayer.in}}</ref>

==Mammalian toxicity/health effects==

Little research has been conducted on the effects of IAA on humans and toxicity data are limited. No data on human carcinogenic, [[Teratology|teratogenic]], or developmental effects have been created.

IAA is listed in its [[Material safety data sheet|MSDS]] as mutagenic to mammalian [[somatic cell]]s, and possibly carcinogenic based on animal data. It may cause adverse reproductive effects (fetotoxicity) and birth defects based on animal data. No human data as of 2008.<ref>[https://www.cdc.gov/niosh-rtecs/NL3010B0.html "1H-Indole-3-acetic acid"] Registry of Toxic Effects of Chemical Substances (RTECS). Page last updated:November 8, 2017.</ref> It is listed as a potential skin, eye, and respiratory irritant, and users are warned not to ingest it. Protocols for ingestion, inhalation, and skin/eye exposure are standard for moderately poisonous compounds and include thorough rinsing in the case of skin and eyes, fresh air in the case of inhalation, and immediately contacting a physician in all cases to determine the best course of action and not to induce vomiting when of ingested. The [[NFPA 704]] health hazard rating for IAA is 2, which denotes a risk of temporary incapacitation with intense or prolonged, but not chronic exposure, and a possibility of residual injury.<ref>[http://www.bio-world.com/site/accounts/masterfiles/MSDS/MS-30631010.pdf "Indole-3-Acetic Acid: Material Safety Data Sheet."] November 2008.</ref> IAA is a direct ligand of the [[aryl hydrocarbon receptor]],<ref>{{Cite journal| doi = 10.1074/jbc.272.52.32824| issn = 1083-351X| volume = 272| issue = 52| pages = 32824–32829| last = Miller| first = Charles A.| title = Expression of the Human Aryl Hydrocarbon Receptor Complex in Yeast ACTIVATION OF TRANSCRIPTION BY INDOLE COMPOUNDS| journal = Journal of Biological Chemistry| access-date = 2020-01-08| date = 1997-12-26| url = http://www.jbc.org/content/272/52/32824| pmid = 9407059| s2cid = 45619222| doi-access = free}}</ref> and IAA treatment of mice indicate liver-protective effects in a model of [[non-alcoholic fatty liver disease]].<ref>{{Cite journal| doi = 10.3390/nu11092062| issn = 2072-6643| volume = 11| issue = 9| last1 = Ji| first1 = Yun| last2 = Gao| first2 = Yuan| last3 = Chen| first3 = Hong| last4 = Yin| first4 = Yue| last5 = Zhang| first5 = Weizhen| title = Indole-3-Acetic Acid Alleviates Nonalcoholic Fatty Liver Disease in Mice via Attenuation of Hepatic Lipogenesis, and Oxidative and Inflammatory Stress| journal = Nutrients| date = 2019-09-03| page = 2062| pmid = 31484323| pmc = 6769627| doi-access = free}}</ref> Humans typically have relatively high levels of IAA in their serum (~1µM), but this can be increased further in certain disease conditions and can be a poor prognostic marker for cardiovascular health.<ref>{{Cite journal| doi = 10.1681/ASN.2013121283| issn = 1533-3450| volume = 26| issue = 4| pages = 876–887| last1 = Dou| first1 = Laetitia| last2 = Sallée| first2 = Marion| last3 = Cerini| first3 = Claire| last4 = Poitevin| first4 = Stéphane| last5 = Gondouin| first5 = Bertrand| last6 = Jourde-Chiche| first6 = Noemie| last7 = Fallague| first7 = Karim| last8 = Brunet| first8 = Philippe| last9 = Calaf| first9 = Raymond| last10 = Dussol| first10 = Bertrand| last11 = Mallet| first11 = Bernard| last12 = Dignat-George| first12 = Françoise| last13 = Burtey| first13 = Stephane| title = The cardiovascular effect of the uremic solute indole-3 acetic acid| journal = Journal of the American Society of Nephrology| date = April 2015| pmid = 25145928| pmc = 4378098}}</ref> Whether this IAA originates from endogenous biosynthesis via IL4I1 or gut [[microbiota]] is unknown. A 2021 study found that normal mice had an average of 3.7 times as much IAA in their feces compared to [[Germ-free_animal|germ-free]] mice, suggesting that the mammalian microbiome contributes significantly to the overall circulating amount. <ref>{{Cite journal| doi =10.1038/s41467-021-26209-8| volume = 12| issue = 6000| last1 = Lai| first1 = Yunjia| last2 = Liu| first2 =Chih-Wei| last3 = Yang| first3 = Yifei| last4 = Hsiao| first4 = Yun-Chung| last5 = Ru| first5 = Hongyu| last6 = Lu| first6 = Kun| title = High-coverage metabolomics uncovers microbiota-driven biochemical landscape of interorgan transport and gut-brain communication in mice.| journal = Nature Communications| date = 2021| page = 6000| pmid = 34667167| pmc = 8526691| bibcode = 2021NatCo..12.6000L| doi-access = free}}</ref>

===Developmental toxicity===

IAA produces [[microcephaly]] in rats during the early stage of cerebral cortex development. IAA treatment of pregnant rats, at a dose of 1 gram per kg of body weight per day, decreased the locomotor activities of rat embryos/fetuses; treatment with IAA and analog 1(methyl)-IAA resulted in apoptosis of neuroepithelial cell and significantly decreased brain sizes relative to body weight in embryonic rats.<ref>{{cite journal |doi=10.2131/jts.30.165 |title=Effect of Indole-3-Acetic Acid Derivatives on Neuroepithelium in Rat Embryos |year=2005 |last1=Furukawa |first1=Satoshi |last2=Usuda |first2=Koji |last3=Abe |first3=Masayoshi |last4=Ogawa |first4=Izumi |journal=The Journal of Toxicological Sciences |volume=30 |issue=3 |pages=165–74 |pmid=16141651|doi-access=free }}</ref>

===Immunotoxin===

IAA is an [[apoptosis]]-inducing ligand in mammals. As of 2010, the [[signal transduction pathway]]s are as follows: IAA/HRP activates [[p38 mitogen-activated protein kinases]] and [[c-Jun N-terminal kinases]]. It induces [[caspase-8]] and [[caspase-9]], which results in [[caspase-3]] activation and [[poly(adp-ribose) polymerases]] cleavage.<ref name=bladder>{{cite journal | vauthors = Jeong YM, Oh MH, Kim SY, Li H, Yun HY, Baek KJ, Kwon NS, Kim WY, Kim DS | year = 2010 | title = Indole-3-acetic acid/horseradish peroxidase induces apoptosis in TCCSUP human urinary bladder carcinoma cells | journal = Pharmazie | volume = 65 | issue = 2| pages = 122–6 | pmid = 20225657 }}</ref>

In 2002 it had been hypothesized that IAA coupled with [[horseradish peroxidase]] (HRP) could be used in targeted cancer therapy. Radical-IAA molecules would attach to cells marked by HRP and HRP reactive cells would be selectively killed.<ref>{{cite journal | author = Wardman P | year = 2002 | title = Indole-3-acetic acids and horseradish peroxidase: a new prodrug/enzyme combination for targeted cancer therapy | journal = Curr. Pharm. Des. | volume = 8 | issue = 15| pages = 1363–74 | pmid = 12052213 | doi = 10.2174/1381612023394610 }}</ref> In 2010 in vitro experiments proved this concept of IAA as an [[immunotoxin]] when used in preclinical studies of targeted cancer therapy, as it induced apoptosis in bladder<ref name=bladder/> and in hematological malignancies.<ref>{{cite journal | vauthors = Dalmazzo LF, Santana-Lemos BA, Jácomo RH, Garcia AB, Rego EM, da Fonseca LM, Falcão RP | year = 2011 | title = Antibody-targeted horseradish peroxidase associated with indole-3-acetic acid induces apoptosis in vitro in hematological malignancies | journal = Leuk. Res. | volume = 35 | issue = 5| pages = 657–62 | doi = 10.1016/j.leukres.2010.11.025 | pmid = 21168913 | s2cid = 32655907 }} cited in: {{cite journal | doi = 10.1182/blood-2014-01-492256 | pmc = 3990911 | pmid=24578503 | volume=123 | title=Immunotoxins for leukemia | year=2014 | vauthors=Wayne AS, Fitzgerald DJ, Kreitman RJ, Pastan I | journal=Blood | issue = 16 | pages=2470–7}}</ref>

==References==

{{Commons category|Indole acetic acid}}

{{Reflist|30em}}

{{Plant hormones}}

{{Authority control}}

[[Category:Auxins]]

[[Category:Plant physiology]]

[[Category:Acetic acids]]

[[Category:Indoles]]

[[Category:Plant growth regulators]]