Molecular actions of nitric oxide in mesangial cells.
Nitric oxide (NO) is a widely recognized mediator of physiological and pathophysiological signal transmission. Its generation through L-arginine metabolism is relevant in the mesangium of the kidney where NO is produced by constitutive and inducible NO-synthase isoenzymes. Signaling is achieved through target interactions via redox and additive chemistry. In mesangial cells (MC), the outcome of these modifications promote on one side activation of soluble guanylyl cyclase while on the other side cytotoxicity is elicited. These contrasting situations are characterized by: 1) cGMP formation and signal propagation towards myosin light chain kinase, the effector system that regulates F-actin assembly, thereby affecting reversible relaxation/contraction of mesangial cells; and 2) initiation of morphological and biochemical alterations that are reminiscent of apoptosis such as chromatin condensation, p53 or Bax accumulation as well as caspase-3 activation. Off note, NO formation with concomitant initiation of apoptosis is efficiently antagonized by the simultaneous presence of superoxide (O2-). We will recall the consequences that stem from a diffusion controlled NO/O2- interaction thereby redirecting the apoptotic initiating activity of either NO or O2- towards protection. The crosstalk between cell destructive and protective signaling pathways, their activation or inhibition under the modulatory influence of NO will be discussed. Here we give examples of how NO elicits physiological and pathophysiological signal transmission in rat MC.
Sandau
K B
KB
Department of Medicine IV, Faculty of Medicine, University of Erlangen-Nürnberg, Germany.
Brüne
B
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D020030:Nitric Oxide Donors; D009569:Nitric Oxide