MAP-kinase dependent activation of kinin B1 receptor gene transcription after heat stress in rat vascular smooth muscle cells.
The mechanism involved in the induction of kinin B1 receptors in pathological situations is not completely defined. In this study, we evaluated whether p42/p44 mitogen activated protein (MAP) and p38 stress activated protein (SAP) kinases were implicated in the activation of the gene encoding for the B1 receptor after heat stress in rat vascular smooth muscle cells (SMCs). Rat vascular SMCs were incubated with either vehicle, or 4(4-fluorophenyl)-2-(4 methylsulfinylphenyl)-5-(4pyridil)imidaz (SB 203580) (10 microM), a selective inhibitor of the p38 SAP kinase pathway or 2-(2amino-3-methoxyphenyl)4H-1-benzopyran-4-one (PD 98059) (25 microM), a selective inhibitor of the p42/p44 MAP kinase pathway and submitted or not to heat stress (42 degrees C, 20 min). Five hours later, B1 receptor mRNA was detected using a semi-quantitative RT-PCR technique. In the meantime, we characterised p42/p44 MAP kinase activation after heat stress by immunodetection. A basal expression of B1 receptor mRNA was detected in rat vascular SMCs. This expression was increased by heat stress. However, in cells previously incubated with either SB 203580 or PD 98059 and submitted to heat stress, this increase in B1 receptor mRNA was not detected. Moreover, we showed by immunodetection that heat stress was followed by a transient phosphorylation of p42/p44 MAP kinases. In conclusion, both p42/p44 and p38 kinases play a crucial role in the mechanism leading to B1 receptor mRNA induction after heat stress.
Lagneux
C
C
Laboratoire du Stress Cardiovasculaire et des Pathologies Associées (LSCPA), Faculté de Pharmacie, Université Joseph Fourier, Domaine de la Merci, 38706 La Tronche, France.
Lebrin
F
F
Demenge
P
P
Godin-Ribuot
D
D
Ribuot
C
C
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation; D006358:Hot Temperature; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D017931:DNA Primers; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases