H and K ions play central roles in prorenin processing and secretion, and prorenin is abnormally expressed in H and K disorders. At the surface membrane of juxtaglomerular (JG) cells, K is sensed and regulated by K channels (coupled to Cl channels and activated by excess Ca), Na-K-adenosinetriphosphatase, and a KCl/H exchange transporter (regulated by Ca). In JG cell granular membrane, K flux is regulated by K channels and a KCl/H exchange transporter (activated by Ca). H channels and a H pump reside in the granular membrane, which maintain H concentration in the granular matrix at least two orders of magnitude greater than in cytosol. The H pump may also be responsible for maintaining the acidic matrix required for maximal prorenin processing to renin by prohormone convertase for human renin (PCren), the prorenin convertase. These molecules form the core of a chemiosmotic system, which appears to regulate both prorenin processing and renin secretion. Renin secretion and prorenin processing appear to be of more than causal significance in clinical disorders characterized by chemiosmotic imbalance. A critical review of the literature supports the following general conclusions. First, hyperrenin state defines the initial phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension. Second, low-renin syndrome defines the transition-to-establish phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension in which the key feature is renin secretory hyporesponsivity. Third, renin disorders are usually associated with other endocrine disorders (polyendocrinopathies types I, II, and III), suggesting that renin may be an important molecule in the processing of chemiosmotic forces. The key chemiosmotic molecules (K and H) are also important in the processing and export of most (if not all) hormones. Thus, by regulating K and H homeostasis, renin may regulate the endocrine system.

Reports on a study which examines the possible mechanisms of renin hyporesponsivity. Description of the phenomenon in diabetes mellitus and other clinical disorders classified along the lines of renin hyporesponsivity; Role of macula densa in the processing of prorenin to renin; Subcellular sites of potential dysregulation in renin secretory hyporesponsivity.

Caspase-3 is a cysteine protease located in both the cytoplasm and mitochondrial intermembrane space that is a central effector of many apoptotic pathways. In resting cells, a subset of caspase-3 zymogens is S-nitrosylated at the active site cysteine, inhibiting enzyme activity. During Fas-induced apoptosis, caspases are denitrosylated, allowing the catalytic site to function. In the current studies, we sought to identify the subpopulation of caspases that is regulated by S-nitrosylation. We report that the majority of mitochondrial, but not cytoplasmic, caspase-3 zymogens contain this inhibitory modification. In addition, the majority of mitochondrial caspase-9 is S-nitrosylated. These studies suggest that S-nitrosylation plays an important role in regulating mitochondrial caspase function and that the S-nitrosylation state of a given protein depends on its subcellular localization.