Welters Hannah J, Diakogiannaki Eleftheria, Mordue J Mark, Tadayyon Moh, Smith Stephen A, Morgan Noel G
Institute of Biomedical and Clinical Science, Peninsula Medical School, Devon, Research Way, Plymouth, PL6 8BU, UK.
Apoptosis. 2006 Jul;11(7):1231-8. doi: 10.1007/s10495-006-7450-7.
Saturated and mono-unsaturated fatty acids exert differential effects on pancreatic beta-cell viability during chronic exposure. Long chain saturated molecules (e.g. palmitate) are cytotoxic to beta-cells and this is associated with caspase activation and induction of apoptosis. By contrast, mono-unsaturated fatty acids (e.g. palmitoleate) are not toxic and can protect against the detrimental effects of palmitate. In the present study, we show that the protective actions of palmitoleate in BRIN-BD11 beta-cells result in attenuated caspase activation following exposure to palmitate and that a similar response occurs in cells having elevated levels of cAMP. However, unlike palmitoleate, elevation of cAMP was unable to prevent the cytotoxic actions of palmitate since it caused a diversion of the pathway of cell death from apoptosis to necrosis. Palmitoleate did not alter cAMP levels in BRIN-BD11 cells and the results suggest that a change in cAMP is not involved in mediating the protective effects of this fatty acid. Moreover, they reveal that attenuated caspase activation does not always correlate with altered cell viability in cultured beta-cells and suggest that mono-unsaturated fatty acids control cell viability by regulating a different step in the apoptotic pathway from that influenced by cAMP.
在长期暴露过程中，饱和脂肪酸和单不饱和脂肪酸对胰腺β细胞的活力产生不同影响。长链饱和分子（如棕榈酸）对β细胞具有细胞毒性，这与半胱天冬酶激活和细胞凋亡诱导有关。相比之下，单不饱和脂肪酸（如棕榈油酸）没有毒性，并且可以抵御棕榈酸的有害影响。在本研究中，我们表明棕榈油酸对BRIN - BD11β细胞的保护作用导致在暴露于棕榈酸后半胱天冬酶激活减弱，并且在cAMP水平升高的细胞中也出现类似反应。然而，与棕榈油酸不同，cAMP升高无法预防棕榈酸的细胞毒性作用，因为它导致细胞死亡途径从凋亡转向坏死。棕榈油酸不会改变BRIN - BD11细胞中的cAMP水平，结果表明cAMP的变化不参与介导这种脂肪酸的保护作用。此外，研究结果表明，在培养的β细胞中，半胱天冬酶激活减弱并不总是与细胞活力改变相关，这表明单不饱和脂肪酸通过调节凋亡途径中与cAMP影响的步骤不同的另一步骤来控制细胞活力。
