Ceramide‐activated protein phosphatase‐2A activity in insulin‐secreting cells

FEBS Letters

Metz, Stewart A¹  Kowluru, Anjaneyulu¹ 

[1] Research and Medical Services, William S. Middleton Memorial VA Medical Center, 2500 Overlook Terrace, Madison, WI 57305, USA

关键词: Pancreatic β cell;    Protein phosphatase 2A;    Okadaic acid;    Ceramide;    Carboxyl methylation;    Apoptosis;   

DOI  :  10.1016/S0014-5793(97)01379-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Okadaic acid (OKA)-sensitive phosphatase (PP2A) activity may modulate nutrient-induced insulin secretion from pancreatic β cells [Kowluru et al., Endocrinology 137 (1996) 2315–2323]. Ceramides, a new class of lipid second messengers may regulate PP2A [Dobrowsky and Hannun, J. Biol. Chem. (1992) 267, 5048–5051], and might play a role in cytokine-mediated apoptosis in β cells [Sjöholm, FEBS Lett. 367 (1995) 283–286]. Therefore, we investigated the regulation of PP2A-like activity by ceramides in isolated β (HIT-T15 or INS-1) cells. Cell-permeable (C2, C6 or C18) ceramides stimulated OKA-sensitive (but not -insensitive) phosphatase activity in a concentration-dependent manner (0–12.5 μM), with maximal stimulation (+50–100%) at <12.5 μM. C2-dihydroceramide (a biologically inactive analog of C2 ceramide) failed to augment PP2A-like activity. Stimulatory effects of ceramides do not appear to be mediated via activation of the carboxyl methylation of the catalytic subunit of protein phosphatase 2A, since no effects of ceramides (up to 25 μM) were demonstrable on this parameter. These data identify a ceramide-activated protein phosphatase as a possible locus at which ceramides might exert their effects on β cells leading to altered insulin secretion, and decreased cell viability followed by apoptotic cell demise.

【 授权许可】

Unknown