Orexin-A Promotes Cell Migration in Cultured Rat Astrocytes via Ca2+-Dependent PKCα and ERK1/2 Signals

Abstract

Orexin-A is an important neuropeptide involved in the regulation of feeding, arousal, energy consuming, and reward seeking in the body. The effects of orexin-A have widely studied in neurons but not in astrocytes. Here, we report that OX1R and OX2R are expressed in cultured rat astrocytes. Orexin-A stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and then induced the migration of astrocytes via its receptor OX1R but not OX2R. Orexin-A-induced ERK1/2 phosphorylation and astrocytes migration are Ca2+-dependent, since they could be inhibited by either chelating the extracellular Ca2+ or blocking the pathway of store-operated calcium entry (SOCE). Furthermore, both non-selective protein kinase C (PKC) inhibitor and PKCα selective inhibitor, but not PKCδ inhibitor, prevented the increase in ERK1/2 phosphorylation and the migration of astrocytes, indicating that the Ca2+-dependent PKCα acts as the downstream of the OX1R activation and mediates the orexin-A-induced increase in ERK1/2 phosphorylation and cell migration. In conclusion, these results suggest that orexin-A can stimulate ERK1/2 phosphorylation and then facilitate the migration of astrocytes via PLC-PKCα signal pathway, providing new knowledge about the functions of the OX1R in astrocytes.

αVβ3 Integrin regulates astrocyte reactivity

“…In addition, the calcium-chelator BAPTA-AM blocks Thy-1-induced hemichannel opening and ATP release, two key steps in the process of Thy-1-induced DITNC1 astrocyte migration [ 21 ]. In agreement with our observations, Fang and coworkers published that Orexin, a neuropeptide that evokes responses similar to those triggered by Thy-1 in astrocytes, induces migration in rat astrocytes in a Ca 2+ -dependent manner, which can be blocked by either the addition of BAPTA-AM or an IP3R blocker, such as 2-APB [ 64 ], supporting the notion that increased [Ca 2+ ] i is necessary for astrocyte migration.…”

Role of orexin A signaling in dietary palmitic acid-activated microglial cells

“…Increased microglial OX1R expression in response to a TLR-4 mediated pro-inflammatory stimulus could represent a compensatory response to reduce the release of inflammatory cytokines. Others have demonstrated that astrocytes, a subset of glial support cells, are responsive to OXA through OX1R by increasing migration following OXA exposure, further indicating OXA is modulatory not only through neuronal cells but also glial cells [32]. Until recently, microglia were thought to be passive support cells, but are now understood to contribute to fine-tuning neural-glial circuitry through cultivating synapses and altering plasticity in healthy and diseased brains [33, 34].…”

Cytotoxic mechanism related to dihydrolipoamide dehydrogenase in Leydig cells exposed to heavy metals

“…_ 8 ) T D $ F I G ] can be divided into three subfamilies: conventional/classical PKCs (a, bI, bII, and g), novel PKCs (d, e, h, and u), and atypical PKCs (z and l) (Huang et al, 2012). It was found that PKCa inhibition robustly attenuated orexin-A-induced ERK1/2 phosphorylation and astrocyte migration, whereas PKCd was not involved in ERK1/2 phosphorylation (Shu et al, 2014). PKA and PKC signaling both contribute to steroidogenesis in Leydig cells (Manna et al, 2007); whereas, the cAMP/PKA pathway is the major signaling cascade in the regulation of trophic hormone-stimulated StAR expression and steroidogenesis (Manna et al, 2009).…”