We report the synthesis of single enantiomers permanently charged dihydropyridine derivatives (DHPs with alkyl linker lengths two and eight carbon atoms) their activities on cardiac neuronal L-type calcium channels. Permanently chiral 1,4-dihydropyridines methyl (ω-trimethylalkylammonium) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate iodides were synthesized in high optical purities from (R)-(−)...

Mitochondrial dysfunction is a significant factor in human disease, ranging from systemic disorders of childhood to cardiomyopathy, ischaemia and neurodegeneration. Cytochrome oxidase, the terminal enzyme mitochondrial respiratory chain, frequent target. Lower eukaryotes possess alternative respiratory-chain enzymes that provide non-proton-translocating bypasses for complexes I (single-subunit reduced nicotinamide adenine dinucleotide dehydrogenases, e.g. Ndi1 yeast) or III + IV [alternative...

Management of chronic obesity-associated metabolic disorders is a key challenge for biomedical researchers. During obesity, visceral adipose tissue (VAT) undergoes substantial transformation characterized by unique lipid-rich hypoxic AT microenvironment (ATenv) which plays crucial role in VAT dysfunction, leading to insulin resistance (IR) and type 2 diabetes(T2D). Here, we demonstrate that obese ATenv triggers the release miR-210-3p microRNA-loaded extracellular vesicles (EVs) from...

Voltage-dependent calcium channels play a role in many cellular phenomena. Very little is known about Ca2+ Drosophila, especially those muscles. Existing literature on neuronal of Drosophila suggests that their pharmacology may be distinct from vertebrate channels. This raises questions the and diversity Here we show channel current body-wall muscles larvae consists two main components. One component sensitive to 1,4-dihydropyridines diltiazem, which block L-type The second amiloride, blocks...

Mangoes (Mangifera indica) are rich in phenolic acids as detected by high-performance liquid chromatography. The phenolics have prominent medicinal properties. Among six important commercial mango cultivars (Deshi, Langra, Chausa, Mallika, Dashahari and Amrapali) tannic acid was maximal while gallic Chausa all other varieties. Caffeic Langra followed Amrapali. Many of the pharmacological properties attributed to might be due presence fairly significant amounts.

Abstract Analysis of the mechanisms underlying cardiac excitability can be faciliated greatly by mutations that disrupt ion channels and receptors involved in this excitability. With an extensive repertoire such mutations, Drosophila provides best available genetic model for these studies. However, use purpose has been severely handicapped lack a suitable preparation heart complete knowledge about ionic currents underlie its We describe simple to measure heartbeat . This was used ask if is...

ABSTRACT The larval muscle fibers of Drosophila show four outward K+ currents in addition to the inward Ca2+ current voltage-clamp recordings. Shaker (Sh) and slowpoke (slo) mutations, respectively, eliminate voltage-activated fast (IA) Ca2+-activated (ICF)-Quinidine specifically blocks delayed (IK) at micromolar concentrations. We used Sh, slo quinidine remove one or more currents, so as study physiological properties these not previously characterized, examine their role membrane...

Mitochondrial dysfunction is involved in many neurodegenerative disorders humans. Here we report mutations a gene (designated levy) that codes for subunit VIa of cytochrome c oxidase (COX). The were identified by the phenotype temperature-induced paralysis and showed additional phenotypes decreased COX activity, age-dependent bang-induced paralysis, progressive neurodegeneration, reduced life span. Germ-line transformation using levy(+) rescued mutant flies from all including...

Selective inhibitors of cyclooxygenase-2 (COX-2), such as rofecoxib (Vioxx), celecoxib (Celebrex), and valdecoxib (Bextra), have been developed for treating arthritis other musculoskeletal complaints. inhibition COX-2 over COX-1 results in preferential decrease prostacyclin production thromboxane A2 production, thus leading to less gastric effects than those seen with nonselective COX acetylsalicylic acid (aspirin). Here we show a novel effect via mechanism that is independent inhibition....

Background Celecoxib (Celebrex), a widely prescribed selective inhibitor of cyclooxygenase-2, can modulate ion channels independently cyclooxygenase inhibition. Clinically relevant concentrations celecoxib affect ionic currents and alter functioning neurons myocytes. In particular, inhibition Kv2.1 by leads to arrhythmic beating Drosophila heart rat cells in culture. However, the spectrum involved human cardiac excitability differs from that animal models, including mammalian making it...

Modulation of calcium channels plays an important role in many cellular processes. Previous studies have shown that the L-type Ca2+ Drosophila larval muscles are modulated via a cAMP-protein kinase A (PKA)-mediated pathway. This raises questions on identity steps prior to cAMP, particularly endogenous signal may initiate this modulatory cascade. We now present data suggesting possible neuropeptide, pituitary adenylyl cyclase-activating polypeptide (PACAP), modulation. Mutations amnesiac...

Paclitaxel (taxol) is a potent anticancer drug that used in the treatment of wide variety cancerous. In present study, we identified taxol derivative named 7-epi-10-deacetyltaxol (EDT) from culture an endophytic fungus Pestalotiopsis microspora isolated bark Taxodium mucronatum. This study was carried out to investigate effects fungal EDT on cell proliferation, induction apoptosis and molecular mechanisms human hepatoma HepG2 cells vitro.The by traditional taxonomical characterization...

ABSTRACT The blockade of K+ channels and enhancement neuromuscular transmission by dendrotoxin (DTX), a convulsant peptide from mamba snake venom, were examined in normal mutant larval preparations Drosophila. Two-microelectrode voltage-clamp experiments showed that DTX reduced the transient current, IA, muscle membrane. This effect was suppressed raising Mg2+ concentration or lowering temperature. interaction with further analyzed at low cation concentration, which both IA delayed rectifier...

The delayed rectifier potassium current plays a critical role in cellular physiology. This (<i>I</i>_K) in<i>Drosophila</i> larvae is believed to be single current. However, likely null mutation the <i>Shab</i>K⁺ channel gene (<i>Shab</i>³) reduces<i>I</i>_K but does not eliminate it. raises question as whether or entire <i>I</i>_Kpasses through channels encoded by one gene. Similarly, an incomplete blockade of <i>I</i>_K high...

Selective cyclooxygenase-2 (COX-2) inhibitors such as rofecoxib (Vioxx) and celecoxib (Celebrex) were developed NSAIDs with reduced gastric side effects. Celecoxib has now been shown to affect cellular physiology via an unexpected, COX-independent, pathway - by inhibiting K(v)2.1 other ion channels. In this study, we investigated the mechanism of action on channels.The mode rat channels was studied whole-cell patch-clamping record currents from expressed in HEK-293 cells.Celecoxib current...