Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20645 (mannose-6-phosphate receptor)
 320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracardiac renin is considered to be involved in the pathogenesis of cardiac hypertrophy, fibrosis, and myocardial infarction. Cardiac renin is predominantly derived from the circulation, because preprorenin is not expressed locally and uptake of renin has been demonstrated. One mechanism of internalization recently described involves the mannose-6-phosphate receptor and requires glycosylation of renin. Based on previous observations, we considered the existence of another pathway of uptake, not requiring glycosylation and predominantly involving prorenin. This hypothesis and its functional consequences were investigated in vitro and in vivo. We demonstrate that isolated adult cardiomyocytes internalize unglycosylated prorenin, which is followed by the generation of angiotensins. We further show that transgenic rats, expressing the ren-2(d) renin gene in an inducible manner, exhibit markedly enhanced levels of unglycosylated renin within intracellular compartments in the heart as a consequence of the induction of hepatic transgene expression and the rise of circulating unglycosylated prorenin levels. Because in this model severe cardiac damage occurs as a consequence of the rise of circulating prorenin levels, internalization of prorenin into cardiac cells is likely to play a key role in this process.
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PMID:Functional significance of prorenin internalization in the rat heart. 1203 5

Renin is commonly known as a secretory glycoprotein, which is expressed, stored and released in a regulated manner by the kidney. Besides this, a number of extrarenal tissues, such as adrenal gland and heart express or internalise renin. In the heart a local RAS may exert prohypertrophic, proliferative, antiproliferative or apoptotic properties. The local RAS in kidney, adrenal gland and heart are each unique and their modes of action are distinct. This is due to the expression of different renin transcripts and different intracellular sorting and transport events for renin. In the rat kidney exclusively the commonly known preprorenin is expressed encoding for secretory renin. This is targeted to lysosomes, which become secretory renin granules. The cells of the rat adrenal cortex express preprorenin as well, but this is partially targeted to the regulated secretory pathway. Rat adrenocortical cells additionally express an alternative renin transcript, termed exon1A renin, which encodes for a truncated prorenin that is imported into mitochondria. Its function is not known to date. Interestingly, in the rat heart exclusively the alternative transcript is expressed. Even in hypertrophic hearts or after myocardial infarction, preprorenin remains undetectable. Exon1A renin transcript levels, in contrast, markedly increased after myocardial ischemia. This provides a new molecular basis for a function of locally expressed renin. In addition, there are different pathways of renin internalisation by cardiac cells. A mannose-6-phosphate receptor mediated uptake has been described. We recently described another pathway independently of the mannose-6-phosphate receptor. Such a pathway is apparently of functional significance. Subsequent generation of angiotensins and myocyte hypertrophy and proliferation by prorenin through angiotensin generation has been described.
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PMID:Intracellular sorting of renin: cell type specific differences and their consequences. 1250 54

The role played by IGF-II in signal transduction through the IGF-II/mannose-6-phosphate receptor (IGF2R) in heart tissue has been poorly understood. In our previous studies, we detected an increased expression of IGF-II and IGF2R in cardiomyocytes that had undergone pathological hypertrophy. We hypothesized that after binding with IGF-II, IGF2R may trigger intracellular signaling cascades involved in the progression of pathologically cardiac hypertrophy. In this study, we used immunohistochemical analysis of the human cardiovascular tissue array to detect expression of IGF2R. In our study of H9c2 cardiomyoblast cell cultures, we used the rhodamine phalloidin staining to measure the cell hypertrophy and western blot to measure the expression of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cells treated with IGF-II. We found that a significant association between IGF2R overexpression and myocardial infarction. The treatment of H9c2 cardiomyoblast cells with IGF-II not only induced cell hypertrophy but also increased the protein level of ANP and BNP. Using Leu27IGF-II, an analog of IGF-II which interacts selectively with the IGF2R, to specifically activate IGF2R signaling cascades, we found that binding of Leu27IGF-II to IGF2R led to an increase in the phosphorylation of protein Kinase C (PKC)-alpha and calcium/calmodulin-dependent protein kinase II (CaMKII) in a Galphaq-dependent manner. By the inhibition of PKC-alpha/CaMKII activity, we found that IGF-II and Leu27IGF-II-induced cell hypertrophy and upregulation of ANP and BNP were significantly suppressed. Taken together, this study provides a new insight into the effects of the IGF2R and its downstream signaling in cardiac hypertrophy. The suppression of IGF2R signaling pathways may be a good strategy to prevent the progression of pathological hypertrophy.
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PMID:IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Galphaq interaction and protein kinase C-alpha/CaMKII activation in H9c2 cardiomyoblast cells. 1843 68