+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Lipotoxic Signaling of Palmitic Acid in Endothelial Cells

, : Lipotoxic Signaling of Palmitic Acid in Endothelial Cells.

Accumulation of palmitic acid (PA) in cells from nonadipose tissues is known to induce lipotoxicity resulting in cellular dysfunction and death. The exact molecular pathways of PA-induced cell death are still mysterious. Here, we show that PA triggers autophagy, which did not counteract but in contrast promoted endothelial cell death. The PA-induced cell death was predominantly necrotic as indicated by annexin V and propidium iodide (PI) staining, absence of caspase activity, low levels of DNA hypoploidy, and an early ATP depletion. In addition PA induced a strong elevation of mRNA levels of ubiquitin carboxyl-terminal hydrolase (CYLD), a known mediator of necroptosis. Moreover, siRNA-mediated knockdown of CYLD significantly antagonized PA-induced necrosis of endothelial cells. In contrast, inhibition and knockdown of receptor interacting protein kinase 1 (RIPK1) had no effect on PA-induced necrosis, indicating the induction of a CYLD-dependent but RIPK1-independent cell death pathway. PA was recognized as a strong and early inducer of autophagy. The inhibition of autophagy by both pharmacological inhibitors and genetic knockdown of the autophagy-specific genes, vacuolar protein sorting 34 (VPS34), and autophagy-related protein 7 (ATG7), could rescue the PA-induced death of endothelial cells. Moreover, the initiation of autophagy and cell death by PA was reduced in endothelial cells loaded with the Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N?,N?-tetraacetic acid-(acetoxymethyl) ester (BAPTA-AM), indicating that Ca2+ triggers the fatal signaling of PA. In summary, we introduce an unexpected mechanism of lipotoxicity in endothelial cells and provide several novel strategies to counteract the lipotoxic signaling of PA.


Other references

Lapouse, R., 1965: Who Is Sick?. American Journal of Orthopsychiatry 35: 138-144

Liu, A.Y.; True, L.D.; Latray, L.; Nelson, P.S.; Ellis, W.J.; Vessella, R.L.; Lange, P.H.; Hood, L.; Van Den Engh, G., 1997: Cell-cell interaction in prostate gene regulation and cytodifferentiation. To examine the role of intercellular interaction on cell differentiation and gene expression in human prostate, we separated the two major epithelial cell populations and studied them in isolation and in combination with stromal cells. The epithel...

Chung, P-Hua.; Cheng, Y., 2016: Prevalence of Self-Reported Work-Related Injuries and Their Association with Psychological Symptoms in General Working Population of Taiwan. NlmCategory="UNASSIGNED">Objectives This study investigated the prevalence of self-reported work-related injuries across occupational groups and examined their association with the risk of psychological symptoms in general working pop...

Rodionov, B.; Argimbaeva, R.; Aiazbaeva, G.; Il'-Iasov, E., 1975: On the turnover of ash elements and nitrogen in Maletum of the Zailiski Alatau. Lesovedenie 3 46-55

Behan, F.C.; Lo, C.Hean.; Shayan, R.; Findlay, M., 2009: The keystone technique for resolution of chronic lower limb wound with lymphoedema. Journal of Plastic, Reconstructive & Aesthetic Surgery 62(5): 701-702

Kapoor H.M., 1975: Pastannah section of Kashmir with special reference to Ophiceras bed of Middlemiss. Journal of the Palaeontological Society of India 20: 339-347

Anonymous, 1953: Toxic chemicals in agriculture. Residues in food. A report of the working party on the extent to which toxic chemical residues in food constitute a risk to the consumer, and their recommendations.

Bowyer, J.F.; Davies, D.L., 1999: Changes in mRNA levels for heat-shock/stress proteins and a secretory vesicle associated cysteine-string protein after amphetamine exposure. Trembly, Bruce [Author], Slikker, William, Jr [Author] Annals of the New York Academy of Sciences; Neuroprotective agents 314-329

Atiyah, M.F.; Hitchin, N.J.; Singer, I.M., 1977: Deformations of instantons. A study is made of the self-dual Yang-Mills fields in Euclidean 4-space. For SU(2) gauge theory it is rigorously shown that the solutions depend on 8k - 3 parameters, where k is the Pontrijagin index.

Randhawa, S.S.; Bajwa, B.S., 1958: Histology of Bud-union in citrus. Blood-red and Jaffa varieties of sweet orange make good union with "Kama Khatta" root-stock in the nursery row. The present studies and experience shows that Jaffa makes compatible union with "Kama Khatta" and is long lived and...