Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, the developmental expression of alpha-, beta- and gamma-subspecies of protein kinase C (PKC) in the rat spinal cord was summarized, and possible roles of this protein for neuronal differentiation were discussed. Faint immunoreactivity (IR) for PKCs was first demonstrated in the cervical spinal cord on embryonic day 13 (E-13). It gradually became stronger, and between E-18 and postnatal day 0 (P-0), strong IR for these three subspecies was uniformly distributed throughout the spinal cord. While thereafter, it irregularly declined, and reached the adult pattern around P-28 or P-35. The motor neurons began to express these three subspecies of PKC in the nucleus, perikaryal cytoplasm, dendrites and axons, soon after they began to differentiate. In the perikaryal cytoplasm, the IR was expressed mainly on ribosomes, and in the dendrites, mainly on cytoskeletal elements. At the late embryonic and early postnatal stages, IR for these PKCs was expressed both in the presynaptic terminals and on the postsynaptic densities. While thereafter, the IR in the former declined, and was detected only on the postsynaptic densities. The dorsal corticospinal tract transiently expressed strong IR for these PKCs at the early postnatal developmental stages, but thereafter, the IR rapidly declined. The developing corticospinal tract fibers expressed strong IR mainly on cytoskeletal elements. In contrast, in the mature fibers, IR for alpha-PKC was detected on some cytoskeletal elements, and for beta-PKC on almost all cytoskeletal elements, but IR for gamma-PKC, mainly on smooth surfaced endoplasmic reticulum. These findings suggest that PKC might be involved in several aspects of neuronal differentiation such as gene expression, protein synthesis, morphological maturation and synapse formation.
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PMID:Subspecies of protein kinase C in the rat spinal cord. 955 Jan 89

Forty-six advanced-stage human breast carcinoma specimens were evaluated by immunohistochemistry for PKC alpha expression and compared with 25 samples of normal adjacent breast tissue. For normal tissue, the median staining of ductal epithelia was of moderate intensity. No staining was observed for 67% of tumor specimens, and only 4% showed intensities greater than the median observed in normal tissue. Faint to moderate PKC alpha staining was observed in the stroma, inflammatory cells, and fibroblasts of tumors but was absent in normal tissue. These findings demonstrate that downregulation of PKC alpha protein occurs in epithelial cells of advanced breast tumors (p<0.001).
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PMID:Immunohistochemical analysis of advanced human breast carcinomas reveals downregulation of protein kinase C alpha. 1496 10

Phorbol esters activate protein kinase C and modulate a variety of downstream cell signaling pathways. 12-O-tetradecanoylphorbol-13-acetate (TPA) is a phorbol ester that induces differentiation or apoptosis in a variety of cell lines at low concentrations. A phase I dose escalation trial of TPA was undertaken for patients with relapsed or refractory malignancies. The starting dose was 0.063 mg/m2 and most patients were treated with an intravenous infusion of TPA on days 1-5 and 8-12 followed by a 2-week rest period prior to retreatment. Thirty-five patients were treated. A biological assay was used to monitor levels of TPA-like activity in the blood after treatment. Serious adverse events included individual episodes of gross hematuria, a grand mal seizure, syncope, and hypotension. Many patients had transient fatigue, mild dyspnea, fever, rigors, and muscular aches shortly after the infusion. Dose-limiting toxicities included syncope and hypotension at a dose of 0.188 mg/m2. Only a single patient had evidence of tumor response. These studies establish 0.125 mg/m2 as the maximally tolerated dose when TPA is administered on this schedule.
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PMID:A phase I clinical trial of 12- O-tetradecanoylphorbol-13-acetate for patients with relapsed/refractory malignancies. 1623 Nov 82

5-fluorouracil is an anti-cancer drug commonly used in oncology practice. Typical side effects are myelosupression, nausea, vomiting, diarrhea and stomatitis. Cardiotoxicity is the other toxicity. Cardiac side effects are ST segment changes, rhythm abnormalities, supraventricular and ventricular dysrhytmias. Pulseless ventricular tachycardia and ventricular fibrillation releated with bolus fluorouracil were not detected in the literature. Here we discussed a 46 year-old male patient that has no known cardiac history. After bolus fluorouracil administration, syncope and pulseless ventricular tachycardia developed in this patient. There are a few explanations about the cardiotoxicity of fluorouracil. One of these is the effect on nitric oxide. It causes a reduction in the levels of endothelial NO and this leads coronary vasospasm. Another explanation is protein kinase C mediated vasospasm. In animal studies toxic myocarditis like lesions were detected with fluorouracil infusions. Finally both myocardit and vasospasm may lead cardiac problems like sudden cardiac deaths. Bolus 5-fluorouracil is as cardiotoxic as 5-fluorouracil infusion and we must be careful about the arrhytmia after the bolus administration.
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PMID:Bolus fluorouracil induced syncope and pulseless ventricular tachycardia: a case report. 2160 46