G proteins-coupled signaling pathways appear to play a role in the development of cardiac hypertrophy and its progression to heart failure. The present study aimed to investigate trimeric G proteins and adenylyl cyclase signaling in immature as well as in adult rat myocardium during this process caused by pressure overload. Pressure overload was induced in newborn (2-day-old) rats by abdominal aortic banding and myocardial preparations from left ventricular myocardium of immature (10-day-old) and adult (90-day-old) animals were analyzed for the relative content of different G protein subunits and adenylyl cyclase (AC) by immunoblotting with specific antibodies. A functional status of the AC signaling system was also evaluated. Normal maturation of rat heart was accompanied by increased expression of AC type V/VI and VII and of the long isoform (G(s)alphaL) of G(s)alpha protein. In parallel, the amounts of myocardial G(i)alpha/G(o)alpha proteins tended to decrease, and G(q)alpha/G(11)alpha and Gbeta did not change. Interestingly, whereas fluoride-stimulated AC activity increased in the course of maturation, activity of AC measured under other experimental conditions (stimulation by Mn2+, forskolin or isoproterenol) was lower in adult than in young rat myocardium. Pressure overload did not influence distribution of G proteins in immature myocardium, but considerably decreased the content of G(s)alphaL and increased G(o)alpha proteins in hearts of 90-day-old rats. These hearts exhibited worsened functional reserve as compared to age-matched controls and activity of AC was also markedly lower. A considerable reduction in Mn(2+)-stimulated AC activity together with similar decrease in AC activity determined under other stimulation conditions suggests that it is a function of AC catalytic subunit that is primarily impaired in this model of pressure overload.

• MeSH
• adenylátcyklasy genetika   metabolismus   MeSH
• exprese genu MeSH
• fluoridy farmakologie   MeSH
• hypertrofie levé komory srdeční metabolismus   MeSH
• isoprenalin farmakologie   MeSH
• kardiomegalie genetika   metabolismus   patologie   MeSH
• kardiotonika farmakologie   MeSH
• kolforsin farmakologie   MeSH
• krysa rodu Rattus MeSH
• mangan farmakologie   MeSH
• myokard metabolismus   MeSH
• novorozená zvířata * MeSH
• potkani Wistar MeSH
• protein - isoformy genetika   metabolismus   MeSH
• proteiny vázající GTP metabolismus   MeSH
• signální transdukce MeSH
• stárnutí MeSH
• tlak * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• adenylátcyklasy MeSH
• fluoridy MeSH
• isoprenalin MeSH
• kardiotonika MeSH
• kolforsin MeSH
• mangan MeSH
• protein - isoformy MeSH
• proteiny vázající GTP MeSH

In vitro experiments suggest that stimulation of lipolysis by catecholamines in adipocytes depends on the energy status of these cells. We tested whether mitochondrial uncoupling proteins (UCPs) that control the efficiency of ATP production could affect lipolysis and noradrenaline signalling in white fat in vivo. The lipolytic effect of noradrenaline was lowered by ectopic UCP1 in white adipocytes of aP2-Ucp1 transgenic mice, overexpressing the UCP1 gene from the aP2 gene promoter, reflecting the magnitude of UCP1 expression, the impaired stimulation of cAMP levels by noradrenaline and the reduction of the ATP/ADP ratio in different fat depots. Thus only subcutaneous but not epididymal fat was affected. UCP1 also down-regulated the expression of hormone-sensitive lipase and lowered its activity, and altered the expression of trimeric G-proteins in adipocytes. The adipose tissue content of the stimulatory G-protein alpha subunit was increased while that of the inhibitory G-protein alpha subunits decreased in response to UCP1 expression. Our results support the idea that the energy status of cells, and the ATP/ADP ratio in particular, modulates the lipolytic effects of noradrenaline in adipose tissue in vivo. They also demonstrate changes at the G-protein level that tend to overcome the reduction of lipolysis when ATP level in adipocytes is low. Therefore, respiratory uncoupling may exert a broad effect on hormonal signalling in adipocytes.

• MeSH
• adenosindifosfát metabolismus   MeSH
• adenosintrifosfát metabolismus   MeSH
• AMP cyklický metabolismus   MeSH
• DNA primery MeSH
• genotyp MeSH
• hepatocyty enzymologie   MeSH
• iontové kanály MeSH
• lipasa genetika   MeSH
• lipolýza * MeSH
• membránové proteiny genetika   fyziologie   MeSH
• mitochondriální proteiny MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• noradrenalin metabolismus   MeSH
• proteiny vázající GTP metabolismus   MeSH
• regulace genové exprese enzymů MeSH
• sekvence nukleotidů MeSH
• transportní proteiny genetika   fyziologie   MeSH
• tuková tkáň enzymologie   metabolismus   MeSH
• uncoupling protein 1 MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosindifosfát MeSH
• adenosintrifosfát MeSH
• AMP cyklický MeSH
• DNA primery MeSH
• iontové kanály MeSH
• lipasa MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• noradrenalin MeSH
• proteiny vázající GTP MeSH
• transportní proteiny MeSH
• Ucp1 protein, mouse MeSH Prohlížeč
• uncoupling protein 1 MeSH