ABSTRACT
Ca2+ pumps are important players in smooth muscle contraction. Nevertheless, little information is available about these pumps in the vas deferens. We have determined which subtype of sarco(endo)plasmic reticulum Ca2+-ATPase isoform (SERCA) is expressed in rat vas deferens (RVD) and its modulation by calmodulin (CaM)-dependent mechanisms. The thapsigargin-sensitive Ca2+-ATPase from a membrane fraction containing the highest SERCA levels in the RVD homogenate has the same molecular mass (∼115 kDa) as that of SERCA2 from the rat cerebellum. It has a very high affinity for Ca2+ (Ca0.5 = 780 nM) and a low sensitivity to vanadate (IC50 = 41 µM). These facts indicate that SERCA2 is present in the RVD. Immunoblotting for CaM and Ca2+/calmodulin-dependent protein kinase II (CaMKII) showed the expression of these two regulatory proteins. Ca2+ and CaM increased serine-phosphorylated residues of the 115-kDa protein, indicating the involvement of CaMKII in the regulatory phosphorylation of SERCA2. Phosphorylation is accompanied by an 8-fold increase of thapsigargin-sensitive Ca2+ accumulation in the lumen of vesicles derived from these membranes. These data establish that SERCA2 in the RVD is modulated by Ca2+ and CaM, possibly via CaMKII, in a process that results in stimulation of Ca2+ pumping activity.
Subject(s)
Animals , Male , Rats , Calcium-Binding Proteins/metabolism , Calcium-Transporting ATPases/metabolism , Calmodulin/metabolism , Protein Serine-Threonine Kinases/metabolism , Vas Deferens/metabolism , Muscle Contraction , Phosphorylation , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolismABSTRACT
The regulatory function of á1B-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na+/K+-ATPase and Ca2+-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant á1B-adrenoceptor (CAMá1B-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca2+-ATPase (PMCA) expression was increased by 30 percent in CAMá1B-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) expression. Moreover, total Ca2+-ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na+/K+-ATPase activity nor the expression of á1 and á2 subunit isoforms was changed in CAMá1B-AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac á1B-AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.
Subject(s)
Animals , Male , Mice , Adenosine Triphosphatases/metabolism , Mitogen-Activated Protein Kinases/metabolism , Myocardium/enzymology , Receptors, Adrenergic, alpha-1/metabolism , Calcium Signaling/physiology , Mice, Transgenic , Up-RegulationABSTRACT
A história da medicina homeopática foi discutida neste artigo, abordando-se as concepçöes de Hipócrates, Galeno, Paracelso e Hahnemann. Pretendemos dar uma idéia da evoluçäo da ciência médica de um modo geral, incluindo, neste contexto, o surgimento gradativo das idéias que levaram Hahnemann a criar a homeopatia.
Subject(s)
Humans , History, Ancient , History, Medieval , History, 19th Century , Homeopathic Remedy , Homeopathy/historyABSTRACT
Os autores apresentam consideraçöes gerais sobre a resposta de imunossupressao associada à moléstia de Chagas, com o objetivo de contribuir para o entendimento deste importante e promissor ramo do conhecimento.
Subject(s)
Humans , Animals , Chagas Disease/immunology , Interleukin-2/immunology , Immune Tolerance/immunology , Acute DiseaseABSTRACT
In order to investigate the effect of mild physical activity on blood pressure (BP), 62 subjects - 21 normotensives (NT) and 41 controlled-hypertensives (CHT) - were submitted to 20 minutes of walking and the evaluation of their systolic, diastolic blood pressure and heart rate (SBP, DBP and HR, respectively) was performed before, during and after exercise. Maximal SBP and DBP values as well as the prevalence of cardiovascular risk factors were also assessed. The results show significant diference between the profile of SBP, DBP and HR response from the NT and CHT, the latter presenting less response than the former (P<0.05). During exercise, maximal SBP and DBP from CHT were not at dangerous levels (mean + - SEM = 148.7 + - 2.5 X 84.7 + - 1.3) corresponding to mild or borderline hypertension. However, other risk factors were detected in the studied group. These findings indicate that hypertension is connected with specific alterations in the control of BP.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Hypertension/classification , Hypertension/physiopathology , Hypertension/therapy , Exercise/physiologyABSTRACT
Após 15 minutos de isquemia, realizada por oclusäo da artéria coronariana, coraçöes de ratos wistar foram reperfundidos por 0-5 hora, 6-11 horas ou 12-17 horas. Apesar das conhecidas características que ocorrem na anoxia miocárdial tal como eosinofilia (acidofilia - dados näo mostrados), edema celular e extracelular, e ondulaçäo das fibras, a alteraçäo mitocondrial foi nosso mais importante achado. A alteraçäo, evidenciada como um alongamento mitocondrial e um aspecto fusiforme, parece ser específi a estas condiçöes experimentais, ou seja, um curto período de hipóxia e um longo período de reperfusäo sanguínea. A razäo deste aspecto näo foi elucidada, mas pode ser devido às trocas peculiares que sofrem as mitocôndrias de tecidos isquêmicos reperfundidos.