Sökning: onr:"swepub:oai:DiVA.org:uu-490389" > Statins Induce Loco...
Fältnamn | Indikatorer | Metadata |
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000 | 07830naa a2201009 4500 | |
001 | oai:DiVA.org:uu-490389 | |
003 | SwePub | |
008 | 221213s2022 | |||||||||||000 ||eng| | |
009 | oai:lup.lub.lu.se:6e69fc6f-6762-47f8-980a-ec0ba947af1e | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4903892 URI |
024 | 7 | a https://doi.org/10.3390/cells112235282 DOI |
024 | 7 | a https://lup.lub.lu.se/record/6e69fc6f-6762-47f8-980a-ec0ba947af1e2 URI |
040 | a (SwePub)uud (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Al-Sabri, Mohamed H.u Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap,Institutionen för farmaceutisk biovetenskap4 aut0 (Swepub:uu)mohal518 |
245 | 1 0 | a Statins Induce Locomotion and Muscular Phenotypes in Drosophila melanogaster That Are Reminiscent of Human Myopathy :b Evidence for the Role of the Chloride Channel Inhibition in the Muscular Phenotypes |
264 | c 2022-11-08 | |
264 | 1 | b MDPI,c 2022 |
338 | a electronic2 rdacarrier | |
520 | a The underlying mechanisms for statin-induced myopathy (SIM) are still equivocal. In this study, we employ Drosophila melanogaster to dissect possible underlying mechanisms for SIM. We observe that chronic fluvastatin treatment causes reduced general locomotion activity and climbing ability. In addition, transmission microscopy of dissected skeletal muscles of fluvastatin-treated flies reveals strong myofibrillar damage, including increased sarcomere lengths and Z-line streaming, which are reminiscent of myopathy, along with fragmented mitochondria of larger sizes, most of which are round-like shapes. Furthermore, chronic fluvastatin treatment is associated with impaired lipid metabolism and insulin signalling. Mechanistically, knockdown of the statin-target Hmgcr in the skeletal muscles recapitulates fluvastatin-induced mitochondrial phenotypes and lowered general locomotion activity; however, it was not sufficient to alter sarcomere length or elicit myofibrillar damage compared to controls or fluvastatin treatment. Moreover, we found that fluvastatin treatment was associated with reduced expression of the skeletal muscle chloride channel, C1C-a (Drosophila homolog of CLCN1), while selective knockdown of skeletal muscle C1C-a also recapitulated fluvastatin-induced myofibril damage and increased sarcomere lengths. Surprisingly, exercising fluvastatin-treated flies restored C1C-a expression and normalized sarcomere lengths, suggesting that fluvastatin-induced myofibrillar phenotypes could be linked to lowered C1C-a expression. Taken together, these results may indicate the potential role of C1C-a inhibition in statinassociated muscular phenotypes. This study underlines the importance of Drosophila melanogaster as a powerful model system for elucidating the locomotion and muscular phenotypes, promoting a better understanding of the molecular mechanisms underlying SIM. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng |
653 | a statins | |
653 | a fluvastatin | |
653 | a statin-induced myopathy | |
653 | a Hmgcr | |
653 | a skeletal muscle chloride channel | |
653 | a C1C-a | |
653 | a CLC-1 | |
653 | a myopathy | |
653 | a locomotion | |
653 | a sarcomere | |
653 | a mitochondrial dysfunction | |
653 | a lipotoxicity | |
653 | a Pkcdelta | |
653 | a Pkc delta | |
653 | a PKCtheta | |
653 | a PKC theta | |
653 | a chelerythrine | |
653 | a Drosophila melanogaster | |
653 | a chelerythrine | |
653 | a CLC-1 | |
653 | a ClC-a | |
653 | a Drosophila melanogaster | |
653 | a fluvastatin | |
653 | a Hmgcr | |
653 | a lipotoxicity | |
653 | a locomotion | |
653 | a mitochondrial dysfunction | |
653 | a myopathy | |
653 | a Pkcdelta (Pkcδ) | |
653 | a PKCtheta (PKCθ) | |
653 | a sarcomere | |
653 | a skeletal muscle chloride channel | |
653 | a statin-induced myopathy | |
653 | a statins | |
700 | 1 | a Behare, Nehau Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut0 (Swepub:uu)nehbe556 |
700 | 1 | a Alsehli, Ahmed M.u Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap,King Abdulaziz Univ & Hosp, Fac Med, Al Ehtifalat St, Jeddah 21589, Saudi Arabia,King Abdulaziz University4 aut0 (Swepub:uu)ahmal312 |
700 | 1 | a Berkins, Samuelu Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut |
700 | 1 | a Arora, Aadeyau Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut |
700 | 1 | a Antoniou, Eiriniu Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut |
700 | 1 | a Moysiadou, Eleni I.u Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut |
700 | 1 | a Anantha-Krishnan, Sowmyau Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut |
700 | 1 | a Cosmen, Patricia D.u Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut |
700 | 1 | a Vikner, Johannau Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut |
700 | 1 | a Moulin, Thiago C.u Uppsala University,Lund University,Lunds universitet,Uppsala universitet,Funktionell farmakologi och neurovetenskap,Lund Univ, Fac Med, Dept Expt Med Sci, Solvegatan 19,BMC F10, S-22184 Lund, Sweden,Associativ inlärning,Forskargrupper vid Lunds universitet,Associative Learning,Lund University Research Groups4 aut0 (Swepub:lu)th3058mo |
700 | 1 | a Ammar, Nourheneu Univ Rennes, Inst Genet & Dev Rennes IGDR, UMR6290, CNRS, F-35065 Rennes, France.,University of Rennes I4 aut |
700 | 1 | a Boukhatmi, Hadiu Univ Rennes, Inst Genet & Dev Rennes IGDR, UMR6290, CNRS, F-35065 Rennes, France.,University of Rennes I4 aut |
700 | 1 | a Clemensson, Laura E.u Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut0 (Swepub:uu)laucl164 |
700 | 1 | a Rask-Andersen, Mathias,d 1979-u Uppsala University,Uppsala universitet,Genomik och neurobiologi4 aut0 (Swepub:uu)matra895 |
700 | 1 | a Mwinyi, Jessicau Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut0 (Swepub:uu)jesmw847 |
700 | 1 | a Williams, Michael J.u Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut0 (Swepub:uu)micwi262 |
700 | 1 | a Fredriksson, Robertu Uppsala University,Uppsala universitet,Institutionen för farmaceutisk biovetenskap4 aut0 (Swepub:uu)rfr20930 |
700 | 1 | a Schiöth, Helgi B.u Uppsala University,Uppsala universitet,Funktionell farmakologi och neurovetenskap4 aut0 (Swepub:uu)helgschi |
710 | 2 | a Uppsala universitetb Funktionell farmakologi och neurovetenskap4 org |
773 | 0 | t Cellsd : MDPIg 11:22q 11:22x 2073-4409 |
856 | 4 | u https://doi.org/10.3390/cells11223528y Fulltext |
856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1718488/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 | u http://dx.doi.org/10.3390/cells11223528x freey FULLTEXT |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-490389 |
856 | 4 8 | u https://doi.org/10.3390/cells11223528 |
856 | 4 8 | u https://lup.lub.lu.se/record/6e69fc6f-6762-47f8-980a-ec0ba947af1e |
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