The Cardioprotective Effect of Metformin in Doxorubicin-Induced Cardiotoxicity: the Role of Autophagy

K

Unique, Specific CART Receptor-Independent Regulatory Mechanism of CART(55-102) Peptide in Spinal Nociceptive Transmission and Its Relation to Dipeptidyl-Peptidase 4 (DDP4)

Cocaine- and amphetamine-regulated transcript (CART) peptides are involved in several physiological and pathological processes, but their mechanism of action is unrevealed due to the lack of identified receptor(s). We provided evidence for the antihyperalgesic effect of CART(55-102) by inhibiting dipeptidyl-peptidase 4 (DPP4) in astrocytes and consequently reducing neuroinflammation in the rat spinal dorsal horn in a carrageenan-evoked inflammation model. Both naturally occurring CART(55-102) and CART(62-102) peptides are present in the spinal cord. CART(55-102) is not involved in acute nociception but regulates spinal pain transmission during peripheral inflammation. While the full-length peptide with a globular motif contributes to hyperalgesia, its N-terminal inhibits this process. Although the anti-hyperalgesic effects of CART(55-102), CART(55-76), and CART(62-76) are blocked by opioid receptor antagonists in our inflammatory models, but not in neuropathic Seltzer model, none of them bind to any opioid or G-protein coupled receptors. DPP4 interacts with Toll-like receptor 4 (TLR4) signalling in spinal astrocytes and enhances the TLR4-induced expression of interleukin-6 and tumour necrosis factor alpha contributing to inflammatory pain. Depending on the state of inflammation, CART(55-102) is processed in the spinal cord, resulting in the generation of biologically active isoleucine-proline-isoleucine (IPI) tripeptide, which inhibits DPP4, leading to significantly decreased glia-derived cytokine production and hyperalgesia

Rizs retinoblasztóma-homológ fehérjék expressziója baktériumban

Előzetes eredmények szerint a lucerna PP2A B” alegysége élesztő két-hibrid rendszerben specifikus kölcsönhatásba lépett a lucerna és a rizs Rb1 fehérjével (Lendvai és mtsai, 2007). Ennek alapján a rizs retinoblasztóma-homológ fehérje (fehérjék) defoszforilációjában is szerepet játszhat ez az enzim. A retinoblasztóma-homológ fehérjék PP2A-val való defoszforilálhatóságának tanulmányozásához E.coliban termeltettem az Rb1 és Rb2 fehérje C-terminális fragmentjét (Rb1/C és Rb2/C), valamint teljes hosszúságú Rb2-t. A pET-28(+) vektor segítségével hexahisztidin fúziós szakasszal együtt expresszálódtak a retinoblasztóma fehérjék, ami lehetővé tette Ni-agaróz kromatográfiával történő tisztításukat. A tisztított fúziós fehérjéket SDS-poliakrilamid gélelektroforézissel és Western blottal vizsgáltam. Az Rb1/C-t közel homogén formában izoláltam, míg az Rb2/C frakciók valamivel több szennyező fehérjét tartalmaztak. Teljes hosszúságú Rb2-t is sikerült kinyerni a baktériumsejtekből, azonban a tisztított frakciók feltehetően az Rb2 proteolitikus bomlástermékeit is tartalmazták.BscBiológi

IL-1[béta] Induced Cytokine Expression by Spinal Astrocytes Can Play a Role in the Maintenance of Chronic Inflammatory Pain

L

Unique, Specific CART Receptor-Independent Regulatory Mechanism of CART(55-102) Peptide in Spinal Nociceptive Transmission and Its Relation to Dipeptidyl-Peptidase 4 (DDP4)

Cocaine- and amphetamine-regulated transcript (CART) peptides are involved in several physiological and pathological processes, but their mechanism of action is unrevealed due to the lack of identified receptor(s). We provided evidence for the antihyperalgesic effect of CART(55-102) by inhibiting dipeptidyl-peptidase 4 (DPP4) in astrocytes and consequently reducing neuroinflammation in the rat spinal dorsal horn in a carrageenan-evoked inflammation model. Both naturally occurring CART(55-102) and CART(62-102) peptides are present in the spinal cord. CART(55-102) is not involved in acute nociception but regulates spinal pain transmission during peripheral inflammation. While the full-length peptide with a globular motif contributes to hyperalgesia, its N-terminal inhibits this process. Although the anti-hyperalgesic effects of CART(55-102), CART(55-76), and CART(62-76) are blocked by opioid receptor antagonists in our inflammatory models, but not in neuropathic Seltzer model, none of them bind to any opioid or G-protein coupled receptors. DPP4 interacts with Toll-like receptor 4 (TLR4) signalling in spinal astrocytes and enhances the TLR4-induced expression of interleukin-6 and tumour necrosis factor alpha contributing to inflammatory pain. Depending on the state of inflammation, CART(55-102) is processed in the spinal cord, resulting in the generation of biologically active isoleucine-proline-isoleucine (IPI) tripeptide, which inhibits DPP4, leading to significantly decreased glia-derived cytokine production and hyperalgesia