PDF(Pubmed)
Abstract：
UNASSIGNED: Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme involved in kidney disease, yet its regulation in diabetic kidney disease (DKD) remains inadequately understood.
UNASSIGNED: Therefore, we investigated the changes of NAD+ levels in DKD and the underlying mechanism.
UNASSIGNED: Alternations of NAD+ levels and its biosynthesis enzymes were detected in kidneys from streptozotocin-induced diabetic mouse model by real-time PCR and immunoblot. The distribution of NAD+ de novo synthetic enzymes was explored via immunohistochemical study. NAD+ de novo synthetic metabolite was measured by LC-MS. Human data from NephroSeq were analyzed to verify our findings.
UNASSIGNED: The study showed that NAD+ levels were decreased in diabetic kidneys. Both mRNA and protein levels of kynurenine 3-monooxygenase (KMO) in NAD+ de novo synthesis pathway were decreased, while NAD+ synthetic enzymes in salvage pathway and NAD+ consuming enzymes remained unchanged. Further analysis of human data suggested KMO, primarily expressed in the proximal tubules shown by our immunohistochemical staining, was consistently downregulated in human diabetic kidneys.
UNASSIGNED: Our study demonstrated KMO of NAD+ de novo synthesis pathway was decreased in diabetic kidney and might be responsible for NAD+ reduction in diabetic kidneys, offering valuable insights into complex regulatory mechanisms of NAD+ in DKD.
UNASSIGNED: Therefore, we investigated the changes of NAD+ levels in DKD and the underlying mechanism.
UNASSIGNED: Alternations of NAD+ levels and its biosynthesis enzymes were detected in kidneys from streptozotocin-induced diabetic mouse model by real-time PCR and immunoblot. The distribution of NAD+ de novo synthetic enzymes was explored via immunohistochemical study. NAD+ de novo synthetic metabolite was measured by LC-MS. Human data from NephroSeq were analyzed to verify our findings.
UNASSIGNED: The study showed that NAD+ levels were decreased in diabetic kidneys. Both mRNA and protein levels of kynurenine 3-monooxygenase (KMO) in NAD+ de novo synthesis pathway were decreased, while NAD+ synthetic enzymes in salvage pathway and NAD+ consuming enzymes remained unchanged. Further analysis of human data suggested KMO, primarily expressed in the proximal tubules shown by our immunohistochemical staining, was consistently downregulated in human diabetic kidneys.
UNASSIGNED: Our study demonstrated KMO of NAD+ de novo synthesis pathway was decreased in diabetic kidney and might be responsible for NAD+ reduction in diabetic kidneys, offering valuable insights into complex regulatory mechanisms of NAD+ in DKD.
摘要：
■烟酰胺腺嘌呤二核苷酸(NAD+)是参与肾脏疾病的关键辅酶,然而，其在糖尿病肾病（DKD）中的调节仍未得到充分理解。
■因此，我们研究了DKD中NAD+水平的变化及其潜在机制。
■通过实时PCR和免疫印迹在链脲佐菌素诱导的糖尿病小鼠模型的肾脏中检测到NAD水平及其生物合成酶的变化。通过免疫组织化学研究探索NAD+从头合成酶的分布。NAD+从头合成代谢物通过LC-MS测量。分析了来自NephroSeq的人类数据以验证我们的发现。
■研究表明，糖尿病肾脏的NAD+水平降低。犬尿氨酸3-单加氧酶(KMO)在NAD+从头合成途径中的mRNA和蛋白水平均降低,而救助途径中的NAD+合成酶和NAD+消耗酶保持不变。对人类数据的进一步分析表明KMO，主要在我们的免疫组织化学染色显示的近端小管中表达，在人类糖尿病肾脏中一直下调。
■我们的研究表明，糖尿病肾脏NAD+从头合成途径的KMO降低，可能是糖尿病肾脏NAD+降低的原因，为DKD中NAD+的复杂调控机制提供有价值的见解。
■因此，我们研究了DKD中NAD+水平的变化及其潜在机制。
■通过实时PCR和免疫印迹在链脲佐菌素诱导的糖尿病小鼠模型的肾脏中检测到NAD水平及其生物合成酶的变化。通过免疫组织化学研究探索NAD+从头合成酶的分布。NAD+从头合成代谢物通过LC-MS测量。分析了来自NephroSeq的人类数据以验证我们的发现。
■研究表明，糖尿病肾脏的NAD+水平降低。犬尿氨酸3-单加氧酶(KMO)在NAD+从头合成途径中的mRNA和蛋白水平均降低,而救助途径中的NAD+合成酶和NAD+消耗酶保持不变。对人类数据的进一步分析表明KMO，主要在我们的免疫组织化学染色显示的近端小管中表达，在人类糖尿病肾脏中一直下调。
■我们的研究表明，糖尿病肾脏NAD+从头合成途径的KMO降低，可能是糖尿病肾脏NAD+降低的原因，为DKD中NAD+的复杂调控机制提供有价值的见解。
