Premium
Ceramide‐activated protein phosphatase‐2A activity in insulin‐secreting cells
Author(s) -
Kowluru Anjaneyulu,
Metz Stewart A
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01379-3
Subject(s) - ceramide , protein phosphatase 2 , okadaic acid , phosphatase , sphingolipid , sphingosine , chemistry , sphingomyelin , microbiology and biotechnology , second messenger system , acid phosphatase , medicine , apoptosis , endocrinology , biology , biochemistry , signal transduction , enzyme , cholesterol , receptor
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.