Ciao Ct ho preso il tuo contatto msn il mio è albyy89@hotmail.it volevo dirti che ho letto su questo forum ed altri dei tuoi post molto interessanti sul AA,
mi avrebbe fatto (TANTO) piacere parlare con te su msn di questa cosa
ti reputo un grande
mi avrebbe fatto (TANTO) piacere parlare con te su msn di questa cosa
ti reputo un grande
"L'acido arachdonico è un acido grasso sintetizzato a partire dall'EPA, dall'acido linoleico e dell'acido gamma-linolenico, tutti acidi grassi della famiglia N-6, grazie all'enzima delta-6-desaturasi.
Dall' AA vengono sintetizzate attraverso le COX 1 e 2 (cicloossigenasi) le sostanze, da molti ritenute "cattive" poichè pro-infiammatori, come le PGF2 . Queste prostaglandine di tipo 2 mediano la risposta infiammatoria.
La risposta pro-infiammatoria, si è visto, è indispensabile per la riparazione e crescita.
Gli utlimi 3 studi mostrano questo.
Il primo invece mostra che lo stimolo dell'angiotensina alla crescita ipertrofica cellulare è media dall'AA.
Angiotensin II-induced ERK1/ERK2 activation and protein synthesis are redox-dependent in glomerular mesangial cells.
Gorin Y, Ricono JM, Wagner B, Kim NH, Bhandari B, Choudhury GG, Abboud HE.
Department of Medicine, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. gorin@uthscsa.edu
Angiotensin II (Ang II) stimulates hypertrophy of glomerular mesangial cells. The signalling mechanism by which Ang II exerts this effect is not precisely known. Downstream potential targets of Ang II are the extracellular-signal-regulated kinases 1 and 2 (ERK1/ERK2). We demonstrate that Ang II activates ERK1/ERK2 via the AT1 receptor. Arachidonic acid (AA) mimics the action of Ang II on ERK1/ERK2 and phospholipase A2 inhibitors blocked Ang II-induced ERK1/ERK2 activation. The antioxidant N-acetylcysteine as well as the NAD(P)H oxidase inhibitors diphenylene iodonium and phenylarsine oxide abolished both Ang II- and AA-induced ERK1/ERK2 activation. Moreover, dominant-negative Rac1 (N17Rac1) blocks activation of ERK1/ERK2 in response to Ang II and AA, whereas constitutively active Rac1 resulted in an increase in ERK1/ERK2 activity. Antisense oligonucleotides for Nox4 NAD(P)H oxidase significantly reduce activation of ERK1/ERK2 by Ang II and AA. We also show that protein synthesis in response to Ang II and AA is inhibited by N17Rac1 or MEK (mitogen-activated protein kinase/ERK kinase) inhibitor. These results demonstrate that Ang II stimulates ERK1/ERK2 by AA and Nox4-derived reactive oxygen species, suggesting that these molecules act as downstream signal transducers of Ang II in the signalling pathway linking the Ang II receptor AT1 to ERK1/ERK2 activation. This pathway involving AA, Rac1, Nox4, reactive oxygen species and ERK1/ERK2 may play an important role in Ang II-induced mesangial cell hypertrophy.
Ibuprofen inhibits skeletal muscle hypertrophy in rats.
Soltow QA, Betters JL, Sellman JE, Lira VA, Long JH, Criswell DS.
Center for Exercise Science, University of Florida, Gainesville, 32611, USA.
PURPOSE: We sought to determine whether cyclooxygenase (COX) activity is necessary for overload-induced growth of adult rat skeletal muscle, and whether nitric oxide synthase (NOS) activity is involved in upregulation of COX messenger RNA (mRNA) expression in skeletal muscle. METHODS: Unilateral surgical removal of the gastrocnemius and soleus was performed on the right hindlimb of 16 female Sprague-Dawley rats (approximately 230 g) to induce chronic overload (OL) of the plantaris for 14 d, with sham surgeries performed on the contralateral leg as a normally loaded (NL) control. Half of the rats were treated with the nonspecific COX inhibitor, ibuprofen (0.2 mg.mL(-1) in drinking water; approximately 20 mg.kg(-1).d(-1)). In a second experiment, the plantaris was unilaterally overloaded for 5 or 14 d in male rats (approximately 350 g; N = 16 rats per time point) and half of the animals were treated with the NOS inhibitor, L-NAME (0.75 mg.mL(-1) in drinking water; approximately 90 mg.kg(-1).d(-1)). RESULTS: Ibuprofen treatment inhibited plantaris hypertrophy by approximately 50% (P < 0.05) following 14 d of OL, as did L-NAME treatment (P < 0.05). COX-1 and COX-2 mRNA did not differ between any groups at 5 d. At 14 d, however, L-NAME caused a 30-fold increase in plantaris COX-1 mRNA expression independent of loading condition. Additionally, OL induced a 20-fold increase in COX-2 mRNA expression compared with NL (P < 0.05) at 14 d, without affecting COX-1 mRNA level. L-NAME treatment significantly inhibited OL-induced expression of COX-2 mRNA. CONCLUSION: COX activity is important for in vivo muscle hypertrophy, and plantaris overload is associated with NOS activity-dependent COX-2 expression.
Prostaglandin F2{alpha} stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway
Valerie Horsley1,2 and Grace K. Pavlath2
1 Graduate Program in Biochemistry, Cell and Developmental Biology
2 Department of Pharmacology, Emory University, Atlanta, GA 30322
Address correspondence to Grace Pavlath, Emory University School of Medicine, Dept. of Pharmacology, Room 5027, O.W. Rollins Research Building, Atlanta, GA 30322. Tel.: [IMG]chrome://skype_ff_toolbar_win/content/cb_transparent_l.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/famfamfam/us.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/arrow.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG](404) 727-3353[IMG]chrome://skype_ff_toolbar_win/content/cb_transparent_r.gif[/IMG]. Fax: (404) 727-0365. E-mail: gpavlat@emory.edu
Skeletal muscle growth requires multiple steps to form large multinucleated muscle cells. Molecules that stimulate muscle growth may be therapeutic for muscle loss associated with aging, injury, or disease. However, few factors are known to increase muscle cell size. We demonstrate that prostaglandin F2{alpha} (PGF2{alpha}) as well as two analogues augment muscle cell size in vitro. This increased myotube size is not due to PGF2{alpha}-enhancing cell fusion that initially forms myotubes, but rather to PGF2{alpha} recruiting the fusion of cells with preexisting multinucleated cells. This growth is mediated through the PGF2{alpha} receptor (FP receptor). As the FP receptor can increase levels of intracellular calcium, the involvement of the calcium-regulated transcription factor nuclear factor of activated T cells (NFAT) in mediating PGF2{alpha}-enhanced cell growth was examined. We show that NFAT is activated by PGF2{alpha}, and the isoform NFATC2 is required for PGF2{alpha}-induced muscle cell growth and nuclear accretion, demonstrating the first intersection between prostaglandin receptor activation and NFAT signaling. Given this novel role for PGF2{alpha} in skeletal muscle cell growth, these studies raise caution that extended use of drugs that inhibit PG production, such as nonsteroidal antiinflammatory drugs, may be deleterious for muscle growth.
Trappe TA, Fluckey JD, White F, Lambert CP, Evans WJ.
Nutrition, Metabolism, and Exercise Laboratory, Donald W. Reynolds Center on Aging, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA. trappetodda@uams.edu
PGs have been shown to modulate skeletal muscle protein metabolism as well as inflammation and pain. In nonskeletal muscle tissues, the over the counter analgesic drugs ibuprofen and acetaminophen function through suppression of PG synthesis. We previously reported that ibuprofen and acetaminophen inhibit the normal increase in skeletal muscle protein synthesis after high intensity eccentric resistance exercise. The current study examined skeletal muscle PG levels in the same subjects to further investigate the mechanisms of action of these drugs in exercised skeletal muscle. Twenty-four males (25 +/- 3 yr) were assigned to 3 groups that received the maximal over the counter dose of ibuprofen (1200 mg/d), acetaminophen (4000 mg/d), or a placebo after 10-14 sets of 10 eccentric repetitions at 120% of concentric 1 repetition maximum using the knee extensors. Preexercise and 24 h postexercise biopsies of the vastus lateralis revealed that the exercise-induced change in PGF(2alpha) in the placebo group (77%) was significantly different (P < 0.05) from those in the ibuprofen (-1%) and acetaminophen (-14%) groups. However, the exercise-induced change in PGE(2) in the placebo group (64%) was only significantly different (P < 0.05) from that in the acetaminophen group (-16%). The exercise-induced changes in PGF(2alpha) and PGE(2) were not different between the ibuprofen and acetaminophen groups. These results suggest that ibuprofen and acetaminophen have a comparable effect on suppressing the normal increase in PGF(2alpha) in human skeletal muscle after eccentric resistance exercise, which may profoundly influence the anabolic response of muscle to this form of exercise."
Dall' AA vengono sintetizzate attraverso le COX 1 e 2 (cicloossigenasi) le sostanze, da molti ritenute "cattive" poichè pro-infiammatori, come le PGF2 . Queste prostaglandine di tipo 2 mediano la risposta infiammatoria.
La risposta pro-infiammatoria, si è visto, è indispensabile per la riparazione e crescita.
Gli utlimi 3 studi mostrano questo.
Il primo invece mostra che lo stimolo dell'angiotensina alla crescita ipertrofica cellulare è media dall'AA.
Angiotensin II-induced ERK1/ERK2 activation and protein synthesis are redox-dependent in glomerular mesangial cells.
Gorin Y, Ricono JM, Wagner B, Kim NH, Bhandari B, Choudhury GG, Abboud HE.
Department of Medicine, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. gorin@uthscsa.edu
Angiotensin II (Ang II) stimulates hypertrophy of glomerular mesangial cells. The signalling mechanism by which Ang II exerts this effect is not precisely known. Downstream potential targets of Ang II are the extracellular-signal-regulated kinases 1 and 2 (ERK1/ERK2). We demonstrate that Ang II activates ERK1/ERK2 via the AT1 receptor. Arachidonic acid (AA) mimics the action of Ang II on ERK1/ERK2 and phospholipase A2 inhibitors blocked Ang II-induced ERK1/ERK2 activation. The antioxidant N-acetylcysteine as well as the NAD(P)H oxidase inhibitors diphenylene iodonium and phenylarsine oxide abolished both Ang II- and AA-induced ERK1/ERK2 activation. Moreover, dominant-negative Rac1 (N17Rac1) blocks activation of ERK1/ERK2 in response to Ang II and AA, whereas constitutively active Rac1 resulted in an increase in ERK1/ERK2 activity. Antisense oligonucleotides for Nox4 NAD(P)H oxidase significantly reduce activation of ERK1/ERK2 by Ang II and AA. We also show that protein synthesis in response to Ang II and AA is inhibited by N17Rac1 or MEK (mitogen-activated protein kinase/ERK kinase) inhibitor. These results demonstrate that Ang II stimulates ERK1/ERK2 by AA and Nox4-derived reactive oxygen species, suggesting that these molecules act as downstream signal transducers of Ang II in the signalling pathway linking the Ang II receptor AT1 to ERK1/ERK2 activation. This pathway involving AA, Rac1, Nox4, reactive oxygen species and ERK1/ERK2 may play an important role in Ang II-induced mesangial cell hypertrophy.
Ibuprofen inhibits skeletal muscle hypertrophy in rats.
Soltow QA, Betters JL, Sellman JE, Lira VA, Long JH, Criswell DS.
Center for Exercise Science, University of Florida, Gainesville, 32611, USA.
PURPOSE: We sought to determine whether cyclooxygenase (COX) activity is necessary for overload-induced growth of adult rat skeletal muscle, and whether nitric oxide synthase (NOS) activity is involved in upregulation of COX messenger RNA (mRNA) expression in skeletal muscle. METHODS: Unilateral surgical removal of the gastrocnemius and soleus was performed on the right hindlimb of 16 female Sprague-Dawley rats (approximately 230 g) to induce chronic overload (OL) of the plantaris for 14 d, with sham surgeries performed on the contralateral leg as a normally loaded (NL) control. Half of the rats were treated with the nonspecific COX inhibitor, ibuprofen (0.2 mg.mL(-1) in drinking water; approximately 20 mg.kg(-1).d(-1)). In a second experiment, the plantaris was unilaterally overloaded for 5 or 14 d in male rats (approximately 350 g; N = 16 rats per time point) and half of the animals were treated with the NOS inhibitor, L-NAME (0.75 mg.mL(-1) in drinking water; approximately 90 mg.kg(-1).d(-1)). RESULTS: Ibuprofen treatment inhibited plantaris hypertrophy by approximately 50% (P < 0.05) following 14 d of OL, as did L-NAME treatment (P < 0.05). COX-1 and COX-2 mRNA did not differ between any groups at 5 d. At 14 d, however, L-NAME caused a 30-fold increase in plantaris COX-1 mRNA expression independent of loading condition. Additionally, OL induced a 20-fold increase in COX-2 mRNA expression compared with NL (P < 0.05) at 14 d, without affecting COX-1 mRNA level. L-NAME treatment significantly inhibited OL-induced expression of COX-2 mRNA. CONCLUSION: COX activity is important for in vivo muscle hypertrophy, and plantaris overload is associated with NOS activity-dependent COX-2 expression.
Prostaglandin F2{alpha} stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway
Valerie Horsley1,2 and Grace K. Pavlath2
1 Graduate Program in Biochemistry, Cell and Developmental Biology
2 Department of Pharmacology, Emory University, Atlanta, GA 30322
Address correspondence to Grace Pavlath, Emory University School of Medicine, Dept. of Pharmacology, Room 5027, O.W. Rollins Research Building, Atlanta, GA 30322. Tel.: [IMG]chrome://skype_ff_toolbar_win/content/cb_transparent_l.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/famfamfam/us.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/arrow.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG][IMG]chrome://skype_ff_toolbar_win/content/space.gif[/IMG](404) 727-3353[IMG]chrome://skype_ff_toolbar_win/content/cb_transparent_r.gif[/IMG]. Fax: (404) 727-0365. E-mail: gpavlat@emory.edu
Skeletal muscle growth requires multiple steps to form large multinucleated muscle cells. Molecules that stimulate muscle growth may be therapeutic for muscle loss associated with aging, injury, or disease. However, few factors are known to increase muscle cell size. We demonstrate that prostaglandin F2{alpha} (PGF2{alpha}) as well as two analogues augment muscle cell size in vitro. This increased myotube size is not due to PGF2{alpha}-enhancing cell fusion that initially forms myotubes, but rather to PGF2{alpha} recruiting the fusion of cells with preexisting multinucleated cells. This growth is mediated through the PGF2{alpha} receptor (FP receptor). As the FP receptor can increase levels of intracellular calcium, the involvement of the calcium-regulated transcription factor nuclear factor of activated T cells (NFAT) in mediating PGF2{alpha}-enhanced cell growth was examined. We show that NFAT is activated by PGF2{alpha}, and the isoform NFATC2 is required for PGF2{alpha}-induced muscle cell growth and nuclear accretion, demonstrating the first intersection between prostaglandin receptor activation and NFAT signaling. Given this novel role for PGF2{alpha} in skeletal muscle cell growth, these studies raise caution that extended use of drugs that inhibit PG production, such as nonsteroidal antiinflammatory drugs, may be deleterious for muscle growth.
Trappe TA, Fluckey JD, White F, Lambert CP, Evans WJ.
Nutrition, Metabolism, and Exercise Laboratory, Donald W. Reynolds Center on Aging, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA. trappetodda@uams.edu
PGs have been shown to modulate skeletal muscle protein metabolism as well as inflammation and pain. In nonskeletal muscle tissues, the over the counter analgesic drugs ibuprofen and acetaminophen function through suppression of PG synthesis. We previously reported that ibuprofen and acetaminophen inhibit the normal increase in skeletal muscle protein synthesis after high intensity eccentric resistance exercise. The current study examined skeletal muscle PG levels in the same subjects to further investigate the mechanisms of action of these drugs in exercised skeletal muscle. Twenty-four males (25 +/- 3 yr) were assigned to 3 groups that received the maximal over the counter dose of ibuprofen (1200 mg/d), acetaminophen (4000 mg/d), or a placebo after 10-14 sets of 10 eccentric repetitions at 120% of concentric 1 repetition maximum using the knee extensors. Preexercise and 24 h postexercise biopsies of the vastus lateralis revealed that the exercise-induced change in PGF(2alpha) in the placebo group (77%) was significantly different (P < 0.05) from those in the ibuprofen (-1%) and acetaminophen (-14%) groups. However, the exercise-induced change in PGE(2) in the placebo group (64%) was only significantly different (P < 0.05) from that in the acetaminophen group (-16%). The exercise-induced changes in PGF(2alpha) and PGE(2) were not different between the ibuprofen and acetaminophen groups. These results suggest that ibuprofen and acetaminophen have a comparable effect on suppressing the normal increase in PGF(2alpha) in human skeletal muscle after eccentric resistance exercise, which may profoundly influence the anabolic response of muscle to this form of exercise."
) a 18 anni sei una MACCHINA di crescita kettenefotte del pgf2.... pensaci a 28-30....
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