Lysophosphatidic acid mediates pleiotropic responses in skeletal muscle cells

• Published in: Biochemical and biophysical research communications Vol. 335; no. 4; pp. 1155 - 1162
• Main Authors: Jean-Baptiste, Gaël, Yang, Zhao, Khoury, Chamel, Greenwood, Michael T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.10.2005
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; APOPTOSIS; Caspase 3; Cell Line; CELL PROLIFERATION; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Survival - physiology; Cell viability; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; GROWTH; Humans; Kidney - drug effects; Kidney - metabolism; LPA; Lysophospholipids - pharmacology; MAP kinase; Mice; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; MUSCLES; PHOSPHOTRANSFERASES; POLYMERASE CHAIN REACTION; RECEPTORS; Receptors, Lysophosphatidic Acid - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Skeletal muscle cells; Caspase 3; MAP kinase; Cell viability; Skeletal muscle cells; LPA
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.08.011

Lysophosphatidic acid (LPA) is a potent modulator of growth, cell survival, and apoptosis. Although all four LPA receptors are expressed in skeletal muscle, very little is known regarding the role they play in this tissue. We used RT-PCR to demonstrate that cultured skeletal muscle C2C12 cells endogenously express multiple LPA receptor subtypes. The demonstration that LPA mediates the activation of ERK1/2 MAP kinase and Akt/PKB in C2C12 cells is consistent with the widely observed mitogenic properties of LPA. In spite of these observations, LPA did not induce proliferation in C2C12 cells. Paradoxically, we found that prolonged treatment of C2C12 cells with LPA led to caspase 3 and PARP cleavage as well as the activation of stress-associated MAP kinases JNK and p38. In spite of these typically pro-apoptotic responses, LPA did not induce cell death. Blocking ERK1/2 and Akt/PKB activation with specific pharmacological inhibitors, nevertheless, stimulated LPA-mediated apoptosis. Taken together, these results suggest that both mitogenic and apoptotic responses serve to counterbalance the effects of LPA in cultured C2C12 cells.