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1.
J. physiol. biochem ; 68(2): 255-262, jun. 2012.
Artigo em Inglês | IBECS | ID: ibc-122345

RESUMO

Aging is associated to oxidative damage and alterations in inflammatory and apoptotic pathways. Aging impairs secretion of several hormones, including melatonin and estrogens. However, the mechanisms involved in aging of smooth muscle are poorly known. We have studied the changes induced by aging in the colonic smooth muscle layer of female rats and the protective effect of hormonal therapy. We used young, aged, and ovariectomized aged female rats. Two groups of ovariectomized rats (22 months old) were treated either with melatonin or with estrogen for 10 weeks before sacrifice. Aging induced oxidative imbalance, evidenced by H2O2 accumulation, lipid peroxidation, and decreased catalase activity. The oxidative damage was enhanced by ovariectomy. In addition, aged colonic muscle showed enhanced expression of the pro-inflammatory enzyme cyclooxygenase 2. Expression of the activated forms of caspases 3 and 9 was also enhanced in aged colon. Melatonin and estrogen treatment prevented the oxidative damage and the activation of caspases. In conclusion, aging of colonic smooth muscle induces oxidative imbalance and activation of apoptotic and pro-inflammatory pathways. Hormonal therapy has beneficial effects on the oxidative and apoptotic changes associated to aging in this model (AU)


Assuntos
Animais , Ratos , Hormônios/farmacocinética , Apoptose , Estresse Oxidativo , Músculo Esquelético , Substâncias Protetoras/farmacocinética , Modelos Animais de Doenças , Terapia de Reposição Hormonal , Envelhecimento
2.
J Physiol Biochem ; 68(2): 255-62, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22167661

RESUMO

Aging is associated to oxidative damage and alterations in inflammatory and apoptotic pathways. Aging impairs secretion of several hormones, including melatonin and estrogens. However, the mechanisms involved in aging of smooth muscle are poorly known. We have studied the changes induced by aging in the colonic smooth muscle layer of female rats and the protective effect of hormonal therapy. We used young, aged, and ovariectomized aged female rats. Two groups of ovariectomized rats (22 months old) were treated either with melatonin or with estrogen for 10 weeks before sacrifice. Aging induced oxidative imbalance, evidenced by H(2)O(2) accumulation, lipid peroxidation, and decreased catalase activity. The oxidative damage was enhanced by ovariectomy. In addition, aged colonic muscle showed enhanced expression of the pro-inflammatory enzyme cyclooxygenase 2. Expression of the activated forms of caspases 3 and 9 was also enhanced in aged colon. Melatonin and estrogen treatment prevented the oxidative damage and the activation of caspases. In conclusion, aging of colonic smooth muscle induces oxidative imbalance and activation of apoptotic and pro-inflammatory pathways. Hormonal therapy has beneficial effects on the oxidative and apoptotic changes associated to aging in this model.


Assuntos
Envelhecimento/efeitos dos fármacos , Colo/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Melatonina/uso terapêutico , Músculo Liso/efeitos dos fármacos , Animais , Caspase 3/metabolismo , Caspase 9/metabolismo , Catalase/metabolismo , Colo/crescimento & desenvolvimento , Colo/metabolismo , Ciclo-Oxigenase 2/metabolismo , Estradiol/análogos & derivados , Estradiol/farmacologia , Estradiol/uso terapêutico , Estrogênios Conjugados (USP)/farmacologia , Estrogênios Conjugados (USP)/uso terapêutico , Feminino , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Melatonina/farmacologia , Músculo Liso/crescimento & desenvolvimento , Músculo Liso/metabolismo , Ovariectomia , Ratos , Ratos Wistar
3.
Curr Med Chem ; 17(34): 4150-65, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20939818

RESUMO

Increases or decreases in the contractile response of smooth muscle underlie important pathological conditions such as hypertension, incontinence and altered gastrointestinal transit. These disorders are also frequently encountered in the aged population. Oxidative stress and inflammation are key features in the initiation, progression, and clinical manifestations of smooth muscle disorders. Melatonin, the major secretory product of the pineal gland, has free radical scavenging and antioxidative properties and protects against oxidative insult. Recently, widespread interest has grown regarding the apparent protective effects of melatonin on smooth muscle dysfunction. "In vitro" studies have shown that melatonin decreased vascular tone of vascular beds from control, hypertensive or aged animals, through the reduction of adrenergic contraction and the increase in acetylcholine-induced relaxation. "In vivo", melatonin also attenuates sympathetic tone by direct activation of melatonin receptors, scavenging free radicals or increasing NO availability in the central nervous system. In the gastrointestinal tract, melatonin treatment improves age-related impairments in gallbladder contractility and prevents deleterious effects of cholecystitis on smooth muscle and the enteric nervous system through suppression of oxidative stress. In addition, melatonin improves colonic transit time in constipation-predominant IBS patients. Melatonin is also able to restore impaired contractility of the detrusor muscle from old animals through normalization of Ca(2+) dependent and independent contraction, mitochondrial polarity, neuromuscular function and oxidative stress, which would explain the effects of melatonin counteracting cystometric changes in senescent animals. It also reverses bladder damage following ischemia/reperfusion. In conclusion, melatonin may be a promising candidate for future research of agents that modulate smooth muscle motility.


Assuntos
Envelhecimento , Antioxidantes , Melatonina , Contração Muscular/efeitos dos fármacos , Músculo Liso , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptores de Melatonina/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Colo/efeitos dos fármacos , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/prevenção & controle , Melatonina/administração & dosagem , Camundongos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Músculo Liso/fisiopatologia , Estresse Oxidativo/fisiologia , Glândula Pineal/fisiopatologia , Ratos , Doenças da Bexiga Urinária/tratamento farmacológico , Doenças da Bexiga Urinária/prevenção & controle
4.
Biochem Pharmacol ; 63(2): 283-92, 2002 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11841804

RESUMO

We studied the role of mitochondria in Ca(2+) signals in fura-2 loaded exocrine pancreatic acinar cells. Mitochondrial depolarization in response to carbonylcyanide-p-tryfluoromethoxyphenyl hydrazone or rotenone (assessed by confocal microscopy using rhodamine-123) induced a partial but statistically significant reduction in the decay of Ca(2+) signals under different experimental conditions. Spreading of Ca(2+) waves evoked by the pancreatic secretagogue cholecystokinin cholecystokinin octapeptide was accelerated by mitochondrial inhibitors, whereas the cytosolic Ca(2+) concentration ([Ca(2+)](i)) oscillations in response to physiological levels of this hormone were suppressed by rotenone and carbonylcyanide-p-tryfluoromethoxyphenyl hydrazone. Oligomycin, an inhibitor of mitochondrial ATP synthase, did no affect either propagation of calcium waves nor [Ca(2+)](i) oscillations. Individual mitochondria of rhod-2 loaded acinar cells showed heterogeneous matrix Ca(2+) concentration increases in response to oscillatory and maximal levels of cholecystokinin octapeptide. On the other hand, using Ba(2+) for unequivocal study of capacitative calcium entry we found that mitochondrial inhibitors did not affect this process. Our results show that although the role of mitochondria as a Ca(2+) clearing system in exocrine cells is quantitatively secondary, they play an essential role in the spatial propagation of Ca(2+) waves and in the development of [Ca(2+)](i) oscillations.


Assuntos
Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Mitocôndrias/fisiologia , Pâncreas/citologia , Animais , Citosol/metabolismo , Técnicas In Vitro , Camundongos , Pâncreas/metabolismo
5.
Biochem Biophys Res Commun ; 271(2): 311-7, 2000 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-10799293

RESUMO

Our objective was to evaluate the role of vacuolar H(+)-ATPase and proton gradients in the refilling of Ca(2+) stores in fura-2-loaded pancreatic acinar cells. Once depleted with a high level of ACh, the Ca(2+) stores were replenished with a Ca(2+)-containing solution. The degree of refilling was estimated with a second release in response to either ACh (ACh-releasable store) or thapsigargin (thapsigargin-releasable store), a specific inhibitor of the endoplasmic reticulum Ca(2+) pumps. Both the protonophore nigericin and folimycin, a specific inhibitor of the vacuolar H(+)-ATPase, reduced reuptake into the ACh-mobilized stores but not into the thapsigargin-releasable pools. These treatments effectively dissipated the subcellular pH gradients (revealed by confocal observation of the distribution of a marker for acidic compartments), and did not impair the [Ca(2+)](i) response to ACh in control cells. Our results indicate that thapsigargin and ACh release heterogeneous Ca(2+) stores which are differently operated by vacuolar proton ATPase.


Assuntos
Cálcio/metabolismo , Macrolídeos , Pâncreas/enzimologia , ATPases Translocadoras de Prótons/fisiologia , Tapsigargina/metabolismo , Vacúolos/enzimologia , Animais , Antibacterianos/farmacologia , Transporte Biológico , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Fura-2/metabolismo , Concentração de Íons de Hidrogênio , Ionóforos/farmacologia , Camundongos , Microscopia Confocal , Nigericina/farmacologia , Prótons , Fatores de Tempo
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