Selective down-regulation of the Cqα/G11α G-protein family in tumour necrosis factor-α induced cell death
摘要：
Investigations into the regulation of heterotrimeric GTP-binding protein a-subunits in models of tumour necrosis factor-α (TNF)-induced cell death, revealed the selective down-regulation of the G q α/G 11 α family of G-proteins. The human HeLa and murine L929 cells treated with recombinant human TNF for up to 24 h displayed down-regulated G q α/G 11 α family protein levels, but not G s α, G i α and G o α protein levels as determined by Western analyses. This effect of TNF was observed in a concentration - and time-dependent manner, consistent with the profiles of TNF-induced cell death observed. Moreover, the functioning of G q α/G 11 α family proteins were found to be impaired in TNF-treated cells, as measured by agonist-induced [Ca 2+ ], i release. In contrast, G s α activity was unaltered by TNF-treatment, determined by measurement of agonist-induced intracellular cyclic AMP generation. These findings in TNF-induced cytotoxic models, indicate a novel 'cross-talk' mechanism by which TNF alters Ca 2+ -signalling mechanisms, which may contribute towards the apoptotic and necrotic cell death.
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DOI：
10.1023/A:1007066409645
被引量：
年份：
2000
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