Biomaterial Database

Transforming growth factor beta and epidermal growth factor alter calcium influx and phosphatidylinositol turnover in rat-1 fibroblasts. 1988

L L Muldoon, and K D Rodland, and B E Magun

Oregon Health Sciences University, Portland 97201.

Transforming growth factor type beta (TGF beta) alters the cellular response to epidermal growth factor (EGF) for a variety of processes ranging from early transport activities and gene transcription to mitogenesis. In order to test the hypothesis that altered signal transduction mechanisms may mediate both the transforming effects of TGF beta and the modulation of EGF-stimulated processes by TGF beta, we have examined second messenger levels in response to growth factor treatment. The addition of EGF or prolonged treatment with TGF beta increased the rate of 45Ca influx in serum-deprived, confluent Rat-1 cells, while the addition of EGF to TGF beta-pretreated cells produced an additive increase in Ca2+ influx. The stimulation of Ca2+ influx by TGF beta was only observed at incubation times greater than 1 h and was inhibited by inclusion of actinomycin D, suggesting that a newly transcribed gene product was required for the observed response to TGF beta. Both EGF and TGF beta displayed similar time and concentration dependencies for stimulation of Ca2+ influx and for accumulation of inositol trisphosphate (IP3). The increase in IP3 accumulation in response to either EGF or TGF beta required the presence of extracellular Ca2+, and the observed concentration dependencies were similar for the stimulation of phosphatidylinositol turnover and Ca2+ influx. The EGF- and TGF beta-stimulated increases in Ca2+ influx could be blocked by cobalt, cadmium, and [ethylenebis(oxyethylenenitrilo)] tetraacetic acid, but not by specific Ca2+ channel blockers such as nifedipine or verapamil, suggesting that these growth factors do not act via L-type voltage-sensitive calcium channels. Those calcium blockers which inhibited Ca2+ influx also inhibited inositol phosphate release. These data, taken together, indicate that Ca2+ influx and inositol phosphate release are coupled in Rat-1 cells and suggest that influx of Ca2+ from the extracellular medium is responsible for the changes in IP3 accumulation observed in response to both EGF and TGF beta.

UI	MeSH Term	Description	Entries
D007295	Inositol Phosphates	Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.	Inositol Phosphate,Phosphate, Inositol,Phosphates, Inositol
D008094	Lithium	An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.	Lithium-7,Lithium 7
D010716	Phosphatidylinositols	Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.	Inositide Phospholipid,Inositol Phosphoglyceride,Inositol Phosphoglycerides,Inositol Phospholipid,Phosphoinositide,Phosphoinositides,PtdIns,Inositide Phospholipids,Inositol Phospholipids,Phosphatidyl Inositol,Phosphatidylinositol,Inositol, Phosphatidyl,Phosphoglyceride, Inositol,Phosphoglycerides, Inositol,Phospholipid, Inositide,Phospholipid, Inositol,Phospholipids, Inositide,Phospholipids, Inositol
D002104	Cadmium	An element with atomic symbol Cd, atomic number 48, and atomic weight 112.41. It is a metal and ingestion will lead to CADMIUM POISONING.
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002712	Chlorides	Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.	Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D003035	Cobalt	A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.	Cobalt-59,Cobalt 59
D003609	Dactinomycin	A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)	Actinomycin,Actinomycin D,Meractinomycin,Cosmegen,Cosmegen Lyovac,Lyovac-Cosmegen,Lyovac Cosmegen,Lyovac, Cosmegen,LyovacCosmegen
D004815	Epidermal Growth Factor	A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.	EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast