Physiological and Pharmacological Role of Lysophosphatidic Acid as Modulator in Mechanotransduction

Abstract

ABSTRACT-The mechanotransduction mechanism is believed to play an important role in maintenance of cellular homeostasis in a wide variety of cell types. In particular, the mechanotransduction system in vascular endothelial cells may be an essential mechanism for local hemodynamic control. Elevations in intracellular free Ca]i) are an important signal in the initial step of mechanotransduction and mechanosensitive (MS) cation channels are thought to be a putative pathway; however, the molecular mechanisms remain unclear. We found that lysophosphatidic acid (LPA), a bioactive phospholipid, sensitizes the response of [Ca 2+ ]i to mechanical stress in several cell types. Employing real-time confocal microscopy, local increases in [Ca 2+ ]i in several regions within the cell during application of mechanical stress were clearly visualized in bovine lens epithelial and endothelial cells in the presence of LPA. The phenomenon was termed "Ca 2+ spots". Pharmacological studies revealed that Ca 2+ spots arise due to influx through MS channels. In this report, our data indicating the possible significance of LPA as an endogenous factor involved in regulation of mechanotransduction is reviewed. Furthermore, our findings suggest that the Ca 2+ spot is a novel phenomenon occurring as an elementary Ca 2+-influx event through MS channels directly coupled with the initial step in mechanotransduction.

Lysophosphatidyl choline modulates mechanosensitive L-type Ca2+ current in circular smooth muscle cells from human jejunum

“…These conformational changes have been linked to mediating ion channel mechanosensitivity (40). Although LPA shares the same tail as LPC, LPA would more likely influence mechanosensitivity of two-pore domain channels, such as the TREK family (32), rather than L-type Ca 2ϩ channels; however, LPA also has been shown to affect intracellular Ca 2ϩ stores (29,30). Choline, entirely missing a fatty acid tail, would reside outside the hydrophobic region.…”

The Mechanosensory Ca2+ Channel as a Central Regulator of Prostate Tumor Cell Migration and Invasiveness

“…On the other hand, they did see enhancement of a LPA-stimulated Ca 2+ influx. Interestingly, LPA also enhances a mechanically induced Ca 2+ influx in a variety of cell types (Ohata et al 2001). Based on this apparent lack of TRPC1-linked SOC activity, Brereton et al (2000) proposed that TRPC1 might form the endogenous cation channel activated by the marine toxin, maitotoxin (MTX).…”

Optical Bioimaging: From Living Tissue to a Single Molecule: Calcium Imaging in Blood Vessel In Situ Employing Two-Photon Excitation Fluorescence Microscopy

“…-influx event through mechanosensitive channels directly coupled with the initial step in mechanotransduction in cultured endothelial (4 -6) and cultured lens epithelial cells (6,7). The Ca 2+ spots, which develop sporadically, exhibit a spatiotemporal pattern distinct from Ca 2+ sparks, the elementary [Ca…”