Personalized Nanotherapy by Specifically Targeting Cell Organelles To Improve Vascular Hypertension

Pala, Rajasekharreddy; Mohieldin, Ashraf M.; Shamloo, Kiumars; Sherpa, Rinzhin T.; Kathem, Sarmed H.; Zhou, Jing; Luan, Zhongyue; Zheng, Jie; Ahsan, Amir; Nauli, Surya M.

doi:10.1021/acs.nanolett.8b04138

Cited by 21 publications

(19 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, functional defects of the cilium, such as dysfunctional polycystins proteins (PC1 or PC2), cause polycystic kidneys 2–4,11,12 . Both PC1 and PC2 form a mechanosensory complex in the cilium, which upon bending modulates calcium fluxes 13,14 .…”

Section: Introductionmentioning

confidence: 99%

Sensory primary cilium is a responsive cAMP microdomain in renal epithelia

Sherpa

Mohieldin

Pala

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

Primary cilia are hair-like cellular extensions that sense microenvironmental signals surrounding cells. The role of adenylyl cyclases in ciliary function has been of interest because the product of adenylyl cyclase activity, cAMP, is relevant to cilia-related diseases. In the present study, we show that vasopressin receptor type-2 (V2R) is localized to cilia in kidney epithelial cells. Pharmacologic inhibition of V2R with tolvaptan increases ciliary length and mechanosensory function. Genetic knockdown of V2R, however, does not have any effect on ciliary length, although the effect of tolvaptan on ciliary length is dampened. Our study reveals that tolvaptan may have a cilia-specific effect independent of V2R or verapamil-sensitive calcium channels. Live-imaging of single cilia shows that V2R activation increases cilioplasmic and cytoplasmic cAMP levels, whereas tolvaptan mediates cAMP changes only in a cilia-specific manner. Furthermore, fluid-shear stress decreases cilioplasmic, but not cytoplasmic cAMP levels. Our data indicate that cilioplasmic and cytoplasmic cAMP levels are differentially modulated. We propose that the cilium is a critical sensor acting as a responsive cAMP microcompartment during physiologically relevant stimuli.

show abstract

Section: Introductionmentioning

confidence: 99%

Sensory primary cilium is a responsive cAMP microdomain in renal epithelia

Sherpa

Mohieldin

Pala

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…[ 110 ] Collectively, precise delivery of NO holds great promises in treating ischemic heart diseases such as myocardium infraction. [ 111 ]…”

Section: The Biomedical Applications Of Polymeric No Delivery Nanoplamentioning

confidence: 99%

“…[110] Collectively, precise delivery of NO holds great promises in treating ischemic heart diseases such as myocardium infraction. [111] In myocardial infarction, infiltration of inflammatory cells such as macrophages and the accompanying inflammatory response are essential for tissue repair. While once it becomes excessive, it will retard wound healing and fall into chronic heart failure.…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

Polymeric Nitric Oxide Delivery Nanoplatforms for Treating Cancer, Cardiovascular Diseases, and Infection

Jin

Gao

Liu

et al. 2020

Adv Healthcare Materials

View full text Add to dashboard Cite

The shortened Abstract is as follows: Therapeutic gas nitric oxide (NO) has demonstrated the unique advances in biomedical applications due to its prominent role in regulating physiological/pathophysiological activities in terms of vasodilation, angiogenesis, chemosensitizing effect, and bactericidal effect. However, it is challenging to deliver NO, due to its short half-life (<5 s) and short diffusion distances (20-160 µm). To address these, various polymeric NO delivery nanoplatforms (PNODNPs) have been developed for cancer therapy, antimicrobial and cardiovascular therapeutics, because of the important advantages of polymeric delivery nanoplatforms in terms of controlled release of therapeutics and the extremely versatile nature. This reviews highlights the recent significant advances made in PNODNPs for NO storing and targeting delivery. The ideal and unique criteria that are required for PNODNPs for treating cancer, cardiovascular diseases and infection, respectively, are summarized. Hopefully, effective storage and targeted delivery of NO in a controlled manner using PNODNPs could pave the way for NO-sensitized synergistic therapy in clinical practice for treating the leading death-causing diseases.

show abstract

“…In this context, one interesting question would be how to target selectively cilium specific AC functions. Recent proof-of concept studies presented nanoparticle-based drug delivery approaches that can specifically target primary cilia in cell culture and animal models [118,119]. Third, the sole means of degrading cAMP are PDEs.…”

Section: Perturbations Of the Camp And Hh Signaling At The Primary CImentioning

confidence: 99%

Hedgehog and Gpr161: Regulating cAMP Signaling in the Primary Cilium

Tschaikner

Enzler

Torres‐Quesada

et al. 2020

Cells

View full text Add to dashboard Cite

Compartmentalization of diverse types of signaling molecules contributes to the precise coordination of signal propagation. The primary cilium fulfills this function by acting as a spatiotemporally confined sensory signaling platform. For the integrity of ciliary signaling, it is mandatory that the ciliary signaling pathways are constantly attuned by alterations in both oscillating small molecules and the presence or absence of their sensor/effector proteins. In this context, ciliary G protein-coupled receptor (GPCR) pathways participate in coordinating the mobilization of the diffusible second messenger molecule 3′,5′-cyclic adenosine monophosphate (cAMP). cAMP fluxes in the cilium are primarily sensed by protein kinase A (PKA) complexes, which are essential for the basal repression of Hedgehog (Hh) signaling. Here, we describe the dynamic properties of underlying signaling circuits, as well as strategies for second messenger compartmentalization. As an example, we summarize how receptor-guided cAMP-effector pathways control the off state of Hh signaling. We discuss the evidence that a macromolecular, ciliary-localized signaling complex, composed of the orphan GPCR Gpr161 and type I PKA holoenzymes, is involved in antagonizing Hh functions. Finally, we outline how ciliary cAMP-linked receptor pathways and cAMP-sensing signalosomes may become targets for more efficient combinatory therapy approaches to counteract dysregulation of Hh signaling.

show abstract

Personalized Nanotherapy by Specifically Targeting Cell Organelles To Improve Vascular Hypertension

Cited by 21 publications

References 42 publications

Sensory primary cilium is a responsive cAMP microdomain in renal epithelia

Sensory primary cilium is a responsive cAMP microdomain in renal epithelia

Polymeric Nitric Oxide Delivery Nanoplatforms for Treating Cancer, Cardiovascular Diseases, and Infection

Hedgehog and Gpr161: Regulating cAMP Signaling in the Primary Cilium

Contact Info

Product

Resources

About