Biochemical and biophysical research communications
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Leptin is a hormone produced by adipocytes that regulates satiety (food uptake) and energy homeostasis by activating receptors expressed in neurons of the hypothalamus. Leptin receptors are also found in other brain regions such as the hippocampus and cerebral cortex, and have known roles in regulating neural development and neuroendocrine functions. ⋯ Activation of the Janus kinase (JAK)-signal transducers and activator of transcription (STAT), phosphatidylinositol (PI) 3-kinase and the extracellular signal regulated kinase (ERK) pathways are known downstream events of leptin receptor signaling, all of which are pro-survival and anti-apoptotic. The relative ease of leptin's accessibility to the brain by peripheral administration makes it a potential drug candidate in the development of therapeutics for brain injuries and neurodegeneration.
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Biochem. Biophys. Res. Commun. · Dec 2007
The expression of receptors for endocannabinoids in human and rodent skeletal muscle.
The endocannabinoid system is a lipid derived signalling system that has been shown to regulate appetite and energy metabolism. The most abundant endogenous endocannabinoid, anandamide, has been shown to activate the cannabinoid receptor type 1 (CB1) and type 2 (CB2) as well as the 'non-cannabinoid' transient receptor potential channel-vanilloid sub-family member 1 (TRPV1), before being rapidly metabolised by fatty acid amide hydrolase (FAAH). ⋯ This suggests that other receptors which are activated by endocannabinoids may be present in skeletal muscle. In this study we describe the presence of not only CB1, but also CB2, TRPV1 and the degrading enzyme FAAH in human and rodent skeletal muscle using reverse transcription polymerase chain reaction (RT-PCR).
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Biochem. Biophys. Res. Commun. · Sep 2007
Rho-kinase phosphorylates eNOS at threonine 495 in endothelial cells.
Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO), which is involved in various physiological functions of the cardiovascular system. eNOS is activated by dephosphorylation at Thr495 and phosphorylation at Ser1177. Inhibition of Rho-kinase, an effector of the small GTPase RhoA, leads to activation of Akt/PKB, which phosphorylates eNOS at Ser1177 and thereby promotes NO production. However, little is known about the effects of Rho-kinase on phosphorylation of Thr495. ⋯ Addition of thrombin to cultured human umbilical vein endothelial cells induced phosphorylation of eNOS at Thr495. Treatment with Y27632, a Rho-kinase inhibitor, suppressed thrombin-induced phosphorylation at Thr495. These results indicate that Rho-kinase can directly phosphorylate eNOS at Thr495 to suppress NO production in endothelium.
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Biochem. Biophys. Res. Commun. · Aug 2007
Expression of transient receptor potential vanilloid 1 (TRPV1) in synovial fibroblasts from patients with osteoarthritis and rheumatoid arthritis.
The transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel, which is mainly expressed by nociceptive neurons in dorsal root and trigeminal ganglia. However, there is increasing evidence that TRPV1 expression is not limited to primary afferent neurons but that the receptor is expressed in various cell types throughout the body. Here, we demonstrate the expression of TRPV1 in synovial fibroblasts (SF) from patients with symptomatic osteoarthritis (OA) and rheumatoid arthritis (RA). ⋯ Stimulation of cultured OA- and RA-SF with the TRPV1 agonist capsaicin led to increased expression of IL-6 mRNA as well as of IL-6 protein in the cell culture supernatants. IL-6 protein expression could be antagonized with capsazepine. Thus, we hypothesize that TRPV1 may play a role in non-neuronal mechanisms that might modulate nociception in symptomatic OA and RA patients.
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Biochem. Biophys. Res. Commun. · Aug 2007
XBP-1, a key regulator of unfolded protein response, activates transcription of IGF1 and Akt phosphorylation in zebrafish embryonic cell line.
The unfolded protein response (UPR) is a conserved and adaptive cellular response to increase cell survival during ER stress. XBP-1 spliced form (XBP-1S) generated by IRE1 endoribonuclease is a key transcriptional regulator in UPR to activate genes involved in protein folding and degradation to restore ER function. Although Akt activation was suggested to be a pro-survival pathway activated during ER stress, the signal to trigger Akt is still not clear. ⋯ In addition, zebrafish IGF1 intron1 with predicted UPRE (XBP-1S binding sites) and ERSE (ATF6/XBP-1S binding site) linked with basal promoter could be activated by XBP-1S, not by XBP-1 unspliced form (XBP-1U). Furthermore, we demonstrate that expression of endogenous IGF1 is transiently induced as XBP-1 splicing during ER stress in parallel to ER chaperone GRP78/Hspa5 and ER resided E3 ubiquitin ligase Synoviolin in ZF4 cells by quantitative PCR. Our results suggest zebrafish XBP-1S not only activates genes responsible for protein folding, transporting, glycosylation and ER associated degradation but also activates anti-apoptosis signal via IGF1/Akt pathway in unfolded protein response to cope with ER stress.