Extracellular matrix inhibits apoptosis and enhances endothelial cell differentiation by a NF?B-dependent mechanism

Abstract

Hormonal and environmental factors that control the growth, differentiation, and regression of the vasculature are of fundamental importance in tumorigenesis and in the choice of therapeutic strategies. To test the hypothesis that estradiol (E2) and basement membrane proteins would affect the survival of vascular endothelial cells (EC), immortalized human umbilical vein endothelial cells (ECV304) were examined for their response to the chemotherapeutic drugs taxol and etoposide. ECV cell apoptosis was inhibited by E2 (taxol only) or attachment to extracellular matrix (ECM) (taxol or etoposide). E2 increased ECV growth, while ECM binding resulted in growth arrest and differentiation. Apoptosis was associated with decreased levels of Bcl-2 and p21 proteins. E2 prevented down-regulation of p21 and Bcl-2 induced by taxol but did not prevent the down-regulation of p21 induced by etoposide, consistent with the failure of E2 to inhibit etoposide-induced cell death. However, ECM prevented p21 and Bcl-2 down-regulation induced by taxol or etoposide. Persistent activation of NFkappaB occurred after attachment of ECV cells to ECM, suggesting a role in survival or differentiation. IkappaBalpha levels were not affected by taxol but were reduced by etoposide treatment, while IkappaBbeta levels did not change with drug treatment. E2 did not alter the levels of IkappaBalpha or IkappaBbeta. Interestingly, levels of IkappaBalpha and IkappaBbeta declined in etoposide-treated ECV cells on ECM concomitant with the elevation of NFkappaB, suggesting that in these cells degradation of IkappaB may be responsible for NFkappaB activation. In agreement with these data, anti-sense NFkappaB treatment of ECV cells inhibited differentiation on ECM, but did not affect cell survival. In conclusion, culture of ECV cells on ECM or treatment with E2 inhibited apoptosis. NFkappaB activation by ECM was necessary for cellular differentiation, rather than inhibition, of apoptosis.

Native low density lipoprotein induces pancreatic β cell apoptosis through generating excess reactive oxygen species

“…These data were similar to those obtained from the platelets prepared from healthy control and diabetic patients (11.9 and 15.6 μmol/4 × 10 7 cells , respectively) [14]. Our previous study using the water-soluble cholesterol also showed the intracellular cholesterol level was increased up to 9.6 μmol/4 × 10 7 cells by free cholesterol loading in MIN6s [14]. This result suggested that the LDLs-loading-induced apoptosis of MIN6s might be cause by the accumulation of intracellular cholesterol that activates the stress signaling and result in apoptosis.…”

“…The LDLs treatment also significantly increased the intracellular cholesterol level up to 10.5 μmol/4 × 10 7 cells , if compared to the 8 μmol/4 × 10 7 cells in control (Figure 4b). These data were similar to those obtained from the platelets prepared from healthy control and diabetic patients (11.9 and 15.6 μmol/4 × 10 7 cells , respectively) [14]. Our previous study using the water-soluble cholesterol also showed the intracellular cholesterol level was increased up to 9.6 μmol/4 × 10 7 cells by free cholesterol loading in MIN6s [14].…”

“…For successful primary culture, they have to culture the islets on extracellular matrix-coated plates. It is reported that the extracellular matrix could inhibit apoptosis by a NF-κB-dependent mechanism [14]. Our previous experience of neuronal primary culture also suggests it.…”

Graded sensitiveness of the various retinal neuron populations on the glyoxal-mediated formation of advanced glycation end products and ways of protection

“…There are hints that vanadium-containing substances can activate the transcription factor NF-κB [16,23,48]. Beneficial effects of vanadate were found in diabetes, e. g., a blood glucose-lowering effect [1,34].…”

Brevican, Neurocan, Tenascin-C, and Tenascin-R Act as Important Regulators of the Interplay Between Perineuronal Nets, Synaptic Integrity, Inhibitory Interneurons, and Otx2

“…It can provide structural support to tissues through the formation of a meshwork consisting of protein–protein and protein–proteoglycan interactions ( Yue, 2014 ). Furthermore, ECM components can serve as ligands for receptors and transmit signals involved in cellular processes such as proliferation, migration, apoptosis, and differentiation ( Wang and Passaniti, 1999 ; Hynes, 2009 ; Padhi and Nain, 2020 ). Although the biochemical composition of the ECM is tissue-specific, the main components are collagens, proteoglycans, and glycoproteins ( Murphy and Rudge, 1985 ; Frantz et al, 2010 ; Maeda, 2015 ).…”