Regulation of urocortin I and its related peptide urocortin II by inflammatory and oxidative stresses in HL-1 cardiomyocytes

Abstract

Despite our knowledge on the regulation of urocortin (Ucn) I and its related peptides in the heart, the possible involvement of cardiovascular stress substances, such as cytokines or angiotensin II (Ang II), on this regulation remains to be fully elucidated. We therefore evaluated the potential role of cardiovascular stress substances on the regulation of the Ucn-corticotropin-releasing hormone (CRH) receptor system in HL-1 cardiomyocytes using a Ucn I-specific RIA, conventional reverse transcription-PCR (RT-PCR) and quantitative real-time RT-PCR. Ucn I mRNA levels were shown to be up-regulated by lipopolysaccarides (LPS), tumor necrosis factor-a (TNF-a), Ang II, H 2 O 2 , and pyrrolidinedithiocarbamate (PDTC). The LPS-and Ang II-induced increase in Ucn I mRNA levels was abolished by tempol. In addition, the secretion of Ucn I from HL-1 cardiomyocytes was stimulated by LPS and TNF-a. On the contrary, Ucn II mRNA was increased by TNF-a alone and Ang II with tempol, and the TNF-a-induced increase in Ucn II mRNA was abolished by erythromycin and PDTC. These results suggested that Ucn I mRNA may be up-regulated by oxidative stress, whereas Ucn II mRNA may be up-regulated by the activated nuclear factor-kB, i.e. inflammatory stress. CRH-R2 mRNA may be negatively regulated by the increase in expression of Ucn I and/or Ucn II mRNA. In conclusion, the Ucn-CRH receptor system may be regulated by two major forms of cardiac stresses, i.e. oxidative and inflammatory stress, and may play a critical role in cardiac stress adaptation in heart diseases.

Urocortins and CRF type 2 receptor isoforms expression in the rat stomach are regulated by endotoxin: role in the modulation of delayed gastric emptying

“…However, other reports showed that glucocorticoids downregulated Ucn 2 expression in the skin and upregulated its expression in the hypothalamus or brain stem (12,13), supporting a tissuespecific glucocorticoid regulation of Ucn 2 as reported for Ucn 1 (30) that needs to be delineated specifically in the stomach. Other mechanisms may involve LPS-related release of cytokines and oxidative stress as demonstrated in Ucn 1 and Ucn 2 gene upregulation by LPS in HL-1 cardiomyocytes (28).…”

Shoc2 Is Targeted to Late Endosomes and Required for Erk1/2 Activation in EGF-Stimulated Cells

“…MP-1 interacts specifically with MEK1 and ERK1, enhances their interaction and recruits these complexes to late endosomes. MP-1 complex is anchored to the endosomal membrane by means of binding to the late-endosomal resident proteins, p14 and p18 [14]. Loss of individual components of the MP-1/p14/p18 complex reduces duration of the ERK1/2 activity, thus implicating late endosomes as an important platform for the ERK1/2 signaling [15].…”

Protective Role of the Neuropeptide Urocortin II against Experimental Sepsis and Leishmaniasis by Direct Killing of Pathogens

“…From an evolutionary perspective, UCNII belongs to one of the oldest peptide lineages conserved between species and regulates stress responses in endocrine, autonomic and immune systems (49, 50). Beside UCNIII, UCNII is the unique member of the CRH family that possesses structural features that are present in the single CRH-like peptide of tunicates and in the insect diuretic peptide (51).…”