Molecular actions of nitric oxide in mesangial cells

Nitric oxide (NO) is a widely recognized mediator of physiological and path ophysiological signal transmission. Its generation through L-arginine metab olism is relevant in the mesangium of the kidney where NO is produced by co nstitutive and inducible NO-synthase isoenzymes. Signaling is achieved thro ugh target interactions via redox and additive chemistry. In mesangial cell s (MC), the outcome of these modifications promote on one side activation o f 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 t hat regulates F-actin assembly, thereby affecting reversible relaxation/con traction of mesangial cells; and 2) initiation of morphological and biochem ical alterations that are reminiscent of apoptosis such as chromatin conden sation, p53 or Bar accumulation as well as caspase-3 activation. Off note, NO formation with concomitant initiation of apoptosis is efficiently antago nized by the simultaneous presence of superoxide (O-2(-)) We will recall, t he consequences that stem from a diffusion controlled NO/O-2(-) interaction thereby redirecting the apoptotic initiating activity of either NO or O-2( -) towards protection. The crosstalk between cell destructive and protectiv e signaling pathways, their activation or inhibition under the modulatory i nfluence of NO will be discussed. Here we give examples of how NO elicits p hysiological and pathophysiological signal transmission in rat MC.