Effects of thiols, sugars, and proteins on nitric oxide activation of guanylate cyclase.
نویسندگان
چکیده
Purification of soluble guanylate cyclase from rat liver resulted in an apparent loss of enzyme activation by nitric oxide that could be restored by dithiothreitol. methemoglobin, bovine serum albumin, or sucrose. Although hemoglobin also permitted some activation with nitric oxide, the effect of other agents to restore enzyme activation was prevented with hemoglobin. As a result of enzyme purification, there is an alteration of the dose-response relationship for nitric oxide activation. After partial enzyme purification, relatively high concentrations of nitric oxide that were stimulatory in crude enzyme preparations had no effect on enzyme activity. However, partially purified or homogeneous enzyme was activated by lower concentrations of nitric oxide. The bell-shaped dose-response curve for nitric oxide was shifted to the left with guanylate cyclase purification. The addition of dithiothreitol, methemoglobin, bovine serum albumin, or sucrose to enzyme markedly broadens the dose-response curve for nitric oxide. Thus, the apparent loss of responsiveness to nitric oxide with purification is a function of increased sensitivity of guanylate cyclase to nitric oxide. Increased sensitivity to nitric oxide with enzyme purification probably results from the removal of heme, proteins, and small molecules that can serve as scavengers or sinks for nitric oxide and prevent excessive oxidation of the enzyme.
منابع مشابه
Nitric oxide and superoxide, a deadly cocktail.
Free radicals and oxidants may have contrasting effects on cells. Nitric oxide is a cellular messenger that acts by several mechanisms, including activation of soluble guanylate cyclase, nitrosylation of thiols, and formation of peroxynitrite. The action of nitric oxide depends on oxidative conditions in the cell. In motor neurons, nitric oxide enhances brain-derived neurotrophic factor effects...
متن کاملAGE proteins as a causative factor in Alzheimer's Disease
The reaction between reducing sugars and protein free amines, known as the Maillar reaction results in the formation of advanced glycation endproducts (AGEs). AGE modification changes the structure of proteins to amyloid cross-beta structure. These protein structures can activate receptors known as RAGE on glial cells (microglia and astrocytes), and induce the expression of inducible nitric oxi...
متن کاملAGE proteins as a causative factor in Alzheimer's Disease
The reaction between reducing sugars and protein free amines, known as the Maillar reaction results in the formation of advanced glycation endproducts (AGEs). AGE modification changes the structure of proteins to amyloid cross-beta structure. These protein structures can activate receptors known as RAGE on glial cells (microglia and astrocytes), and induce the expression of inducible nitric oxi...
متن کاملThe Effects of Nitroxyl (HNO) on Soluble Guanylate Cyclase Activity
It has been previously proposed that nitric oxide (NO) is the only biologically relevant nitrogen oxide capable of activating the enzyme soluble guanylate cyclase (sGC). However, recent reports implicate HNO as another possible activator of sGC. Herein, we examine the affect of HNO donors on the activity of purified bovine lung sGC and find that, indeed, HNO is capable of activating this enzyme...
متن کاملPost-translational regulation of endothelial nitric oxide synthase in vascular endothelium
Nitric oxide (NO) is a short-lived gaseous signaling molecule. In blood vessels, it is synthesized in a dynamic fashion by endothelial nitric oxide synthase (eNOS) and influences vascular function via two distinct mechanisms, the activation of soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)-dependent signaling and the S-nitrosylation of proteins with reactive thiols (S-nitr...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 254 24 شماره
صفحات -
تاریخ انتشار 1979