Biology subjects

Kaul, S.

Publications and source records attributed to Kaul, S..

3 recordsLinked to original sources

bioRxiv2018

Bidirectional Control of Coronary Vascular Resistance by Eicosanoids via a Novel GPCR

Arachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We identified G protein-coupled receptor 39 (GPR39) as a microvascular smooth muscle cell (mVSMC) receptor antagonistically regulated by two endogenous eicosanoids: 15-HETE, which stimulates GPR39 to increase mVSMC intracellular calcium and augment microvascular CVR, and 14,15-EET, which inhibits these actions. Furthermore, zinc ion acts as an allosteric modulator of GPR39 to potentiate the efficacy of the two ligands. Our findings will have a major impact on understanding the roles of eicosanoids in cardiovascular physiology and disease, and provide an opportunity for the development of novel GPR39-targeting therapies for cardiovascular disease.\n\nOne Sentence SummaryGPR39 is a microvascular smooth muscle cell receptor regulated by two vasoactive eicosanoids with opposing actions.

physiology↗

bioRxiv2018

PCPE2 and SR-BI Partner to Impact Accumulation of Fat in Mice

LDL receptor knockout mice (LDLr-/-) were crossed with PCPE2 knockout mice to obtain Ldlr-/-,Pcpe2-/- mice. The rationale of these studies was to examine the effects of an extracellular matrix protein, PCPE2, on fat storage in a dyslipidemic mouse model. Male Ldlr-/-, Pcpe2-/- mice were fed a Western diet for 25 weeks and their plasma triglyceride metabolism and triglyceride storage was examined. Interestingly, visceral but not subcutaneous fat pad were smaller in diet-fed Ldlr-/-,Pcpe2-/- mice compared to controls. There was no difference in the fatty acid distribution in triglyceride and cholesteryl esters (CE) among the genotypes. Ldlr-/-, Pcpe2-/- mice have higher plasma triglyceride levels and reduced lipoprotein lipase activity. Immunoprecipitation of SR-BI from cell extracts co-precipitated PCPE2 suggesting that PCPE2 and SR-BI are tightly associated. This work also showed that in the absence of PCPE2 SR-BI does not transfer CE from HDL into the cell. These results suggest that HDL, PCPE2, SR-BI, and possibly LPL are associated in an interactome that is required for CE transport into the cell. In the absence of these interactions lipid transport is significantly disrupted.

biochemistry↗

bioRxiv2017

Neuronal Patterning Of The Tubular Collar Cord Is Highly Conserved Among Enteropneusts But Dissimilar To The Chordate Neural Tube

The dorsal neural tube of chordates and the ventral nerve cord of annelids exhibit a similar molecular mediolateral architecture. Accordingly, the presence of such a complex nervous system (CNS) has been proposed for their last common ancestor. Members of Enteropneusta, a group of non-chordate deuterostomes, possess a less complex CNS including a hollow neural tube, whereby homology to its chordate counterpart remains elusive. Since the majority of data on enteropneusts stem from Saccoglossus kowalevskii, a derived direct-developer, we investigated expression of key neuronal patterning genes in the indirect-developer Balanoglossus misakiensis.\n\nThe collar cord of B. misakiensis shows anterior Six3/6 and posterior Otx + engrailed expression, in a region corresponding to the chordate brain. Neuronal Nk2.1/Nk2.2 expression is absent. Interestingly, we found median Dlx and lateral Pax6 expression domains, i.e., a condition that is reversed compared to chordates.\n\nComparative analyses reveal that CNS patterning is highly conserved among enteropneusts. BmiDlx and BmiPax6 have no corresponding expression domains in the chordate brain, which may be indicative of independent acquisition of a tubular CNS in Enteropneusta and Chordata. Moreover, mediolateral architecture varies considerably among chordates and enteropneusts, questioning the presence of a vertebrate-like patterned nervous system in the last common deuterostome ancestor.

evolutionary biology↗