Lipid signaling

Source: Wikipedia, the free encyclopedia.
platelet activating factor (PAF)
anandamide
or arachidonoyl ethanolamine (AEA)

Lipid signaling, broadly defined, refers to any biological

vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum
.

Sphingolipid second messengers

Main articles: second messenger system and sphingolipid
Sphingolipid second messengers. Ceramide is at the metabolic hub, leading to the formation of other sphingolipids.

Ceramide

diacylglycerol (DAG) from PC.[citation needed
]

erythrocytes).[6] However, ceramide can possibly interact with other lipids to form bigger regions called microdomains which restrict its flip-flopping abilities. This could have immense effects on the signaling functions of ceramide because it is known that ceramide generated by acidic SMase enzymes in the outer leaflet of an organelle membrane may have different roles compared to ceramide that is formed in the inner leaflet by the action of neutral SMase enzymes.[7]

glucocorticoids or obesity.[23]

An increase in in vitro activity of acid SMase has been observed after applying multiple stress stimuli such as

plasma membrane and the simultaneous formation of ceramide.[24]

enzymes in distinct organelles by particular mechanisms at various times.[27]

Sphingosine

lysosomes. It is proposed that the role of SK1 located near or in the lysosome is to ‘trap’ Sph via phosphorylation.[31]

It is important to note that since sphingosine exerts

macrophages. Treatment of the same cells by exogenous Sph caused apoptosis. A specific protein kinase phosphorylates 14-3-3, otherwise known as sphingosine-dependent protein kinase 1 (SDK1), only in the presence of Sph.[32]

Sph is also known to interact with protein targets such as the

second messenger function of Sph is not yet established unambiguously.[34]

Sphingosine-1-Phosphate

immune complexes.[31]

S1P is probably formed at the inner leaflet of the plasma membrane in response to TNFα and other receptor activity-altering compounds called

lipoproteins.[42] Inside the cell, S1P can induce calcium release independent of the S1PRs—the mechanism of which remains unknown. To date, the intracellular molecular targets for S1P are still unidentified.[31]

The SK1-S1P pathway has been extensively studied in relation to cytokine action, with multiple functions connected to effects of

neurodegenerative disorders.[31]

Glucosylceramide

chemotherapeutic agents.[48][49] For instance, a study demonstrated a correlation between cellular drug resistance and modifications in GluCer metabolism.[50]

In addition to their role as building blocks of biological membranes,

glycosphingolipids have long attracted attention because of their supposed involvement in cell growth, differentiation, and formation of tumors.[31] The production of GluCer from Cer was found to be important in the growth of neurons or brain cells.[51] On the other hand, pharmacological inhibition of GluCer synthase is being considered a technique to avoid insulin resistance.[52]

Ceramide-1-Phosphate

Ceramide-1-phosphate (C1P) is formed by the action of ceramide kinase (CK) enzymes on Cer. C1P carry ionic charge at neutral pH and contain two hydrophobic chains making it relatively insoluble in aqueous environment. Thus, C1P reside in the organelle where it was formed and is unlikely to spontaneously flip-flop across membrane bilayers.[31]

C1P activate

vesicular trafficking, cell survival, phagocytosis ("cell eating") and macrophage degranulation.[56][57]

Phosphatidylinositol bisphosphate (PIP2) Lipid Agonist

PIP2 binds directly to ion channels and modulates their activity. PIP2 was shown to directly agonizes

Kir).[58] In this regard intact PIP2 signals as a bona fide neurotransmitter-like ligand.[59] PIP2's interaction with many ion channels suggest that the intact form of PIP2 has an important signaling role independent of second messenger signaling.[citation needed
]

Second messengers from phosphatidylinositol

Phosphatidylinositol bisphosphate (PIP2) Second Messenger Systems

Cartoon of second messenger systems. Figure adapted From Barbraham Institute Mike Berridge. https://web.archive.org/web/20090323190124/http://www.babraham.ac.uk/emeritus/berridge.html (accessed Jan. 21, 2008).

A general second messenger system mechanism can be broken down into four steps. First, the agonist activates a membrane-bound receptor. Second, the activated G-protein produces a primary effector. Third, the primary effect stimulates the second messenger synthesis. Fourth, the second messenger activates a certain cellular process.

The

Diacylglycerol
(DAG).

IP3 is soluble and diffuses freely into the cytoplasm. As a second messenger, it is recognized by the inositol triphosphate receptor (IP3R), a Ca2+ channel in the endoplasmic reticulum (ER) membrane, which stores intracellular Ca2+. The binding of IP3 to IP3R releases Ca2+ from the ER into the normally Ca2+-poor cytoplasm, which then triggers various events of Ca2+ signaling. Specifically in blood vessels, the increase in Ca2+ concentration from IP3 releases nitric oxide, which then diffuses into the smooth muscle tissue and causes relaxation.[34]

DAG remains bound to the membrane by its fatty acid "tails" where it recruits and activates both conventional and novel members of the protein kinase C family. Thus, both IP3 and DAG contribute to activation of PKCs.[60][61]

phosphatidylinositol bisphosphate (PIP2) to produce phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 has been shown to activate protein kinase B, increase binding to extracellular proteins and ultimately enhance cell survival.[34]

Activators of G-protein coupled receptors

See main article on

G-protein coupled receptors

Lysophosphatidic acid (LPA)

G-protein coupled receptors LPA1, LPA2, and LPA3 (also known as EDG2, EDG4, and EDG7, respectively).[citation needed
]

Sphingosine-1-phosphate (S1P)

G-protein coupled receptors, S1P1 - S1P5. Targeted deletion of S1P1 results in lethality in mice and deletion of S1P2 results in seizures and deafness. Additionally, a mere 3- to 5-fold elevation in serum S1P concentrations induces sudden cardiac death by an S1P3
-receptor specific mechanism.

Platelet activating factor (PAF)

G-protein coupled receptor
, PAFR and is inactivated by PAF acetylhydrolase.

Endocannabinoids

The endogenous

analgesia and anti-inflammation and tissue protection during states of ischemia, but the precise roles played by these various endocannabinoids are still not totally known and intensive research into their function, metabolism, and regulation is ongoing. One saturated lipid from this class, often called an endocannabinoid, but with no relevant affinity for the CB1 and CB 2 receptor is palmitoylethanolamide. This signaling lipid has great affinity for the GRP55 receptor and the PPAR alpha receptor. It has been identified as an anti-inflammatory compound already in 1957, and as an analgesic compound in 1975. Rita Levi-Montalcini
first identified one of its biological mechanisms of action, the inhibition of activated mast cells. Palmitoylethanolamide is the only endocannabinoid available on the market for treatment, as a food supplement.

Prostaglandins

Main article:
Eicosanoids

G-protein coupled receptors (eicosanoid receptors) that largely mediate prostaglandin physiology (although some prostaglandins activate nuclear receptors
, see below).

FAHFA

FAHFAs (fatty acid esters of hydroxy fatty acids) are formed in adipose tissue, improve glucose tolerance and also reduce adipose tissue inflammation. Palmitic acid esters of hydroxy-stearic acids (PAHSAs) are among the most bioactive members able to activate

G-protein coupled receptors 120.[63] Docosahexaenoic acid ester of hydroxy-linoleic acid (DHAHLA) exert anti-inflammatory and pro-resolving properties.[64]

Retinol derivatives

Main article: visual cycle

GPCR that binds all-cis retinal in its inactive state. Upon photoisomerization by a photon the cis-retinal is converted to trans-retinal causing activation of rhodopsin which ultimately leads to depolarization of the neuron thereby enabling visual perception
.

Activators of nuclear receptors

See the main article on nuclear receptors

Steroid Hormones

This large and diverse class of

progestogens
.

Retinoic acid

nuclear receptors such as the RAR to control differentiation and proliferation of many types of cells during development.[65]

Prostaglandins

Main article:
Eicosanoids

The majority of

PPAR family. (See article eicosanoid receptors
for more information).

See also

References

  1. S2CID 19898617
    .
  2. S2CID 20973940
    .
  3. PMID 16229686
    .
  4. PMID 16170208
    .
  5. PMID 16905542
    .
  6. PMID 15883154
    .
  7. PMID 15052326
    .
  8. ^ Obeid, L. M., Linardic, C. M., Karolak, L. A. & Hannun, Y. A. (1993) Programmed cell death induced by ceramide. Science. 259, 1769–1771 .
  9. PMID 8530509
    .
  10. PMID 14657198
    .
  11. PMID 7877980
    .
  12. PMID 8662781
    .
  13. PMID 9094715
    .
  14. PMID 7744003
    .
  15. PMID 11723139
    .
  16. PMID 14739942
    .
  17. PMID 15901738
    .
  18. PMID 7634330
    .
  19. PMID 10722759
    .
  20. PMID 12578840
    .
  21. PMID 9632728
    .
  22. PMID 12960011
    .
  23. PMID 17339025
    .
  24. ^
    PMID 15849201
    .
  25. S2CID 4406741
    .
  26. PMID 17591919
    .
  27. S2CID 8692993
    .
  28. PMID 16996023
    .
  29. PMID 12815058
    .
  30. PMID 1898331
    .
  31. ^ a b c d e f g h Hannun and Obeid (2008)
  32. PMID 12893264
    .
  33. PMID 11070884
    .
  34. ^
    S2CID 10765956
    .
  35. PMID 17416206
    .
  36. PMID 9826677
    .
  37. ^
    S2CID 8966010
    .
  38. S2CID 46727063
    .
  39. PMID 15158755
    .
  40. PMID 17050692
    .
  41. PMID 11443135
    .
  42. PMID 12069820
    .
  43. PMID 17280869
    .
  44. S2CID 22184217
    .
  45. S2CID 8617384
    .
  46. PMID 9695839
    .
  47. S2CID 4387982
    .
  48. ^ Radin, N. S., Shayman, J.A. & Inokuchi, J.-I. Metabolic effects of inhibiting glucosylceramide synthesis with PDMP and other substances. Adv. Lipid Res. 26, 183–211
  49. PMID 17010304
    .
  50. PMID 8702646
    .
  51. PMID 9096129
    .
  52. PMID 17287460
    .
  53. PMID 14676210
    .
  54. PMID 14523050
    .
  55. PMID 12416995
    .
  56. PMID 15899891
    .
  57. S2CID 33693599
    .
  58. PMID 21874019
    .
  59. PMID 25633344
    .
  60. PMID 1318060
    .
  61. S2CID 31065063
    .
  62. PMID 25684574
    .
  63. PMID 25303528
    .
  64. PMID 27313314
    .
  65. PMID 18805086
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Lipid_signaling&oldid=1215352408"