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The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia.

ABSTRACT: As recombinant tissue plasminogen activator is the only drug approved for the clinical treatment of acute ischemic stroke, there is an urgent unmet need for novel stroke treatments. Endogenous defense mechanisms against stroke may hold the key to new therapies for stroke. A large number of studies suggest that nicotinamide phosphoribosyl-transferase (NAMPT is an attractive candidate to improve post-stroke recovery. NAMPT is a multifunctional protein and plays important roles in immunity, metabolism, aging, inflammation, and stress responses. NAMPT exists in both the intracellular and extracellular space. As a rate-limiting enzyme, the intracellular form (iNAMPT catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD from nicotinamide. iNAMPT closely regulates energy metabolism, enhancing the proliferation of endothelial cells, inhibiting apoptosis, regulating vascular tone, and stimulating autophagy in disease conditions such as stroke. Extracellular NAMPT (eNAMPT is also known as visfatin (visceral fat-derived adipokine and has pleotropic effects. It is widely believed that the diverse biological functions of eNAMPT are attributed to its NAMPT enzymatic activity. However, the effects of eNAMPT on ischemic injury are still controversial. Some authors have argued that eNAMPT exacerbates ischemic neuronal injury non-enzymatically by triggering the release of TNF-? from glial cells. In addition, NAMPT also participates in several pathophysiological processes such as hypertension, atherosclerosis, and ischemic heart disease. Thus, it remains unclear under what conditions NAMPT is beneficial or destructive. Recent work using in vitro and in vivo genetic/ pharmacologic manipulations, including our own studies, has greatly improved our understanding of NAMPT. This review focuses on the multifaceted and complex roles of NAMPT under both normal and ischemic conditions.

SUBMITTER: Chen X

PROVIDER: S-EPMC5644507 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia.

Chen Xinzhi X Zhao Shangfeng S Song Yang Y Shi Yejie Y Leak Rehana K RK Cao Guodong G

Current topics in medicinal chemistry 20150101 21

As recombinant tissue plasminogen activator is the only drug approved for the clinical treatment of acute ischemic stroke, there is an urgent unmet need for novel stroke treatments. Endogenous defense mechanisms against stroke may hold the key to new therapies for stroke. A large number of studies suggest that nicotinamide phosphoribosyl-transferase (NAMPT is an attractive candidate to improve post-stroke recovery. NAMPT is a multifunctional protein and plays important roles in immunity, metabol ...[more]

PMID: 26059356

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Project description:BACKGROUND:Postoperative hypophosphatemia is common and is associated with a lower risk of liver failure after hepatectomy, but higher morbidity after pancreatectomy. Whether different physiologic mechanisms underlie the hypophosphatemia associated with these very different clinical outcomes is unclear. This study aims to evaluate the underlying mechanism in postoperative hypophosphatemia. STUDY DESIGN:We prospectively enrolled 120 patients who underwent major hepatectomy (n = 30), minor hepatectomy (n = 30), pancreatectomy (n = 30), and laparotomy without resection (control group, n = 30). Preoperative and postoperative serum and urinary phosphorus, calcium, and creatinine, as well as phosphaturic factors, including serum nicotinamide phosphoribosyltransferase (NAMPT), fibroblast growth factor-23, and parathyroid hormone were measured. In addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide. RESULTS:We found that significant hypophosphatemia occurred from postoperative day (POD) 1 to POD 2 in all 4 groups and was preceded by hyperphosphaturia from preoperative day to POD 1. Phosphate level alterations were associated with a significant increase in NAMPT levels from preoperative day to POD 2 in all 3 resected groups, but not in the control group. The fibroblast growth factor-23 levels were significantly decreased postoperatively in all 4 groups, and parathyroid hormone levels did not change in any of the 4 groups. Urine levels of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide decreased significantly in all 4 groups postoperatively. CONCLUSIONS:This study demonstrates that the mechanism of hypophosphatemia is the same for both liver and pancreas resections. Postoperative hypophosphatemia is associated with increased NAMPT. The mechanism that upregulates NAMPT and its role on disparate clinical outcomes in postoperative patients warrant additional investigation.

Dataset Information

The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia.

Publications

The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia.

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