José Santos-Alvarez

Publications (3)0 Total impact

• Chapter: Regulation of the Immune Response by Leptin

  Víctor Sánchez-Margalet, Patricia Fernández-Riejos, Carmen González-Yanes, Souad Najib, Consuelo Martín-Romero, José Santos-Alvarez
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  ABSTRACT: Adipose tissue is no longer considered as a mere energy store, but an important endocrine organ that produces many signals in a tightly regulated manner. Leptin is one of the most important hormones secreted by the adipocyte, with a variety of physiological roles related with the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. Leptin’s modulation of the immune system is exerted at the development, proliferation, anti-apoptotic, maturation, and activation levels. The role of leptin in regulating the immune response has been assessed in vitro as well as in clinical studies. Both the innate and adaptive immune responses are regulated by leptin. Every cell type involved in immunity can be modulated by leptin. In fact, leptin receptors have been found in neutrophils, monocytes, and lymphocytes, and the leptin receptor belongs to the family of class I cytokine receptors. Moreover, leptin activates similar signaling pathways to those engaged by other members of the family. The overall leptin action in the immune system is a proinflammatory effect, activating proinflammatory cells, promoting T-helper 1 responses, and mediating the production of other proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-2, or IL-6. Leptin receptor is also upregulated by proinflammatory signals. Thus, leptin is a mediator of the inflammatory response, and could have also a permissive role in the development of autoimmune diseases.
  12/2006: pages 79-90;
• Chapter: Pancreastatin

  Victor Sánchez-Margalet, Carmen González-Yanes, José Santos-Alvarez, Souad Najib
  12/2001: pages 247-262;
• Article: Pancreastatin, a chromogranin A-derived peptide, activates Gα16 and phospholipase C-β2 by interacting with specific receptors in rat heart membranes

  Carmen González-Yanes, José Santos-Alvarez, Vı́ctor Sánchez-Margalet
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  ABSTRACT: Pancreastatin (PST) is one of the chromogranin A (CGA)-derived peptides with known biological activity. It has a general inhibitory effect on secretion in many exocrine and endocrine systems including the heart atrium. Besides, a role of PST as a counter-regulatory peptide of insulin action has been proposed in the light of its effects on glucose and lipid metabolism in the liver and adipose tissue, where receptors and signaling have been described. Gαq/11 pathway seems to mediate PST action. Since PST has been shown to function as a typical calcium-dependent hormone, and increased plasma levels have been found in essential hypertension correlating with catecholamines, we sought to study its possible interaction and signaling in heart membranes. Here, we are characterizing specific PST binding sites and signaling in rat heart membranes. We have found that PST receptor has a Kd of 0.5 nM and a Bmax of 34 fmol/mg of protein. The PST binding is inhibited by guanine nucleotides, suggesting the functional coupling of the receptor with GTP binding proteins (G proteins). Moreover, PST dose-dependently increases GTP binding to rat heart membranes. Finally, we have studied PST signaling-effector system by measuring phospholipase C (PLC) activity using blocking antibodies against different G proteins and PLC isoforms. We have found that PST stimulates PLCβ2>PLCβ1>PLCβ3 by activating Gα16 in rat heart membranes. These data suggest that PST may modulate the cardiac function.
  Cellular Signalling.