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Total 736 results found since Jan 2013.

Loss of sphingosine kinase 2 protects against cisplatin induced-kidney injury
Am J Physiol Renal Physiol. 2022 Jul 14. doi: 10.1152/ajprenal.00229.2021. Online ahead of print.ABSTRACTCisplatin is an established chemotherapeutic drug for treatment of solid-organ cancers, and is the primary drug utilized in the treatment of head and neck cancer; however, cisplatin-induced nephrotoxicity largely limits its clinical use. Inhibition of sphingosine kinase 2 (SphK2) has been demonstrated to alleviate various kidney diseases. Therefore, we hypothesized that inhibition of SphK2 could also protect against cisplatin-induced nephrotoxicity. Results from the present study showed that the SphK2 inhibitor, ABC2946...
Source: American Journal of Physiology. Renal Physiology - July 14, 2022 Category: Physiology Authors: Dengpiao Xie Gaizun Hu Chaoling Chen Fereshteh Ahmadinejad Weili Wang Pin-Lan Li David A Gewirtz Ningjun Li Source Type: research

Signal Peptide Features Determining the Substrate Specificities of Targeting and Translocation Components in Human ER Protein Import
In human cells, approximately 30% of all polypeptides enter the secretory pathway at the level of the endoplasmic reticulum (ER). This process involves cleavable amino-terminal signal peptides (SPs) or more or less amino-terminal transmembrane helices (TMHs), which serve as targeting determinants, at the level of the precursor polypeptides and a multitude of cytosolic and ER proteins, which facilitate their ER import. Alone or in combination SPs and TMHs guarantee the initial ER targeting as well as the subsequent membrane integration or translocation. Cytosolic SRP and SR, its receptor in the ER membrane, mediate cotransl...
Source: Frontiers in Physiology - July 11, 2022 Category: Physiology Source Type: research

Role of SNARE Proteins in the Insertion of KCa3.1 in the Plasma Membrane of a Polarized Epithelium
Targeting proteins to a specific membrane is crucial for proper epithelial cell function. KCa3.1, a calcium-activated, intermediate-conductance potassium channel, is targeted to the basolateral membrane (BLM) in epithelial cells. Surprisingly, the mechanism of KCa3.1 membrane targeting is poorly understood. We previously reported that targeting of KCa3.1 to the BLM of epithelial cells is Myosin-Vc-, Rab1-and Rab8-dependent. Here, we examine the role of the SNARE proteins VAMP3, SNAP-23 and syntaxin 4 (STX-4) in the targeting of KCa3.1 to the BLM of Fischer rat thyroid (FRT) epithelial cells. We carried out immunoblot, siRN...
Source: Frontiers in Physiology - June 27, 2022 Category: Physiology Source Type: research

Post-Ganglionic Sympathetic Neurons can Directly Sense Raised Extracellular Na+ via SCN7a/Nax
The relationship between dietary NaCl intake and high blood pressure is well-established, and occurs primarily through activation of the sympathetic nervous system. Nax, a Na+-sensitive Na+ channel, plays a pivotal role in driving sympathetic excitability, which is thought to originate from central regions controlling neural outflow. We investigated whether post-ganglionic sympathetic neurons from different ganglia innervating cardiac and vasculature tissue can also directly sense extracellular Na+. Using whole-cell patch clamp recordings we demonstrate that sympathetic neurons from three sympathetic ganglia (superior cerv...
Source: Frontiers in Physiology - June 17, 2022 Category: Physiology Source Type: research

Hypoxic pulmonary endothelial cells release epidermal growth factor leading to vascular smooth muscle cell arginase ‐2 expression and proliferation
We hypothesized that the release of epidermal growth factor (EGF) by human pulmonary microvascular endothelial cells (hPMVEC) could result in the proliferation of human pulmonary arterial smooth muscle cells via activation of the EGF receptor (EGFR) on the hPASMC leading to Arg2 up-regulation. Our data suggest that hypoxic hPMVEC do release EGF, which activates hPASMC EGFR leading to Arg2 protein expression and an increase in viable smooth muscle cell numbers. AbstractThe hallmark of pulmonary hypertension (PH) is vascular remodeling. We have previously shown that human pulmonary microvascular endothelial cells (hPMVEC) re...
Source: Physiological Reports - June 9, 2022 Category: Physiology Authors: Bernadette Chen, Yi Jin, Caitlyn M. Pool, Yusen Liu, Leif D. Nelin Tags: ORIGINAL ARTICLE Source Type: research

Belumosudil, ROCK2-Specific Inhibitor, alleviates cardiac fibrosis by inhibiting cardiac fibroblasts activation
In conclusion, Belumosudil may be a promising therapeutic drug for cardiac hypertrophy and fibrosis induced by myocardial pressure overload.PMID:35657612 | DOI:10.1152/ajpheart.00014.2022
Source: American Journal of Physiology. Heart and Circulatory Physiology - June 3, 2022 Category: Physiology Authors: Quan Liu Hua-Yang Li Shun-Jun Wang Sui-Qing Huang Yuan Yue Adilai Maihemuti Yi Zhang Lin Huang Li Luo Kang-Ni Feng Zhong-Kai Wu Source Type: research