Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Whole exome sequencing (WES) was used in the research of familial pulmonary arterial hypertension (FPAH).
CAV1
and
KCNK3
were found as two novel candidate genes of FPAH. However, few pathogenic genes were identified in idiopathic pulmonary arterial hypertension (IPAH). We conducted WES in 20 unrelated IPAH patients who did not carry the known PAH-pathogenic variants among
BMPR2
,
CAV1
,
KCNK3
,
SMAD9
,
ALK1
, and
ENG
. We found a total of 4,950 variants in 3,534 genes, including 4,444 single-nucleotide polymorphisms and 506 insertions/deletions (InDels). Through the comprehensive and multilevel analysis, we disclosed several novel signaling cascades significantly connected to IPAH, including variants related to cadherin signaling pathway, dilated cardiomyopathy, glucose metabolism, immune response,
mucin
-type
O
-glycosylation,
phospholipase C
(
PLC
)-activating G protein-coupled receptor (GPCR) signaling pathway, vascular contraction and generation, and voltage-dependent Ca
2+
channels. We also conducted validation studies in five mutant genes related to
PLC
-activating GPCR signaling pathway potentially involved in intracellular calcium regulation through Sanger sequencing for mutation accuracy, qRT-PCR for mRNA stability, immunofluorescence for subcellular localization, Western blotting for protein level, Fura-2 imaging for intracellular calcium, and proliferation analysis for cell function. The validation experiments showed that those variants in
CCR5
and
C3AR1
significantly increased the rise of intracellular calcium and the variant in
CCR5
profoundly enhanced proliferative capacity of human pulmonary artery smooth muscle cells. Thus, our study suggests that multiple genetically affected signaling pathways take effect together to cause the formation of IPAH and the development of right heart failure and may further provide new therapy targets or putative clues for the present treatments such as limited therapeutic effectiveness of Ca
2+
channel blockers.
...
PMID:Comprehensive identification of signaling pathways for idiopathic pulmonary arterial hypertension. 3215 64
Mucin secretion from conjunctival goblet cells forms the tear film
mucin
layer and requires regulation to function properly. Maresin 1 (MaR1) is a specialized proresolving mediator produced during the resolution of inflammation. We determined if MaR1 stimulates
mucin
secretion and signaling pathways used. Cultured rat conjunctival goblet cells were used to measure the increase in intracellular Ca
2+
([Ca
2
+
]
i
) concentration and
mucin
secretion. MaR1-increased [Ca
2+
]
i
and secretion were blocked by inhibitors of
phospholipase C
, protein kinase C, Ca
2+
/calmodulin-dependent protein kinase II, and extracellular-regulated kinase 1/2. MaR1 added before addition of histamine counterregulated histamine-stimulated increase in [Ca
2+
]
i
and secretion. We conclude that MaR1 likely has two actions in conjunctival goblet cells: first, maintaining optimal tear film
mucin
levels by increasing [Ca
2+
]
i
and stimulating
mucin
secretion in health and, second, attenuating the increase in [Ca
2+
]
i
and overproduction of
mucin
secretion by counterregulating the effect of histamine as occurs in ocular allergy.
...
PMID:Maresin 1, a specialized proresolving mediator, stimulates intracellular [Ca
2+
] and secretion in conjunctival goblet cells. 3251 Jun 63
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