Potential Therapeutic Role of L-Carnitine in Skeletal Muscle Oxidative Stress and Atrophy Conditions

<div>CARN action on neoformed myotubes. To study CARN action on C2C12 myotubes, neoformed myotubes (after 72 h to differentiation induction) were stimulated for 24 h with 5 mM CARN. Graphs of Western blot analysis during postdifferentiation phase show the significant increment of MyHC protein level in neoformed myotubes treated with CARN. In addition, CARN increases IGF-1 receptor and activates AKT and pp70S6 protein kinases. Representative immunoblots of analyzed proteins are shown. Significance: <svg height="15.2434pt" id="M85" style="vertical-align:-3.9935pt" version="1.1" viewbox="-0.0498162 -11.2499 57.4165 15.2434" width="57.4165pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0095,0,0,-0.0095,0,-5.984)"><path d="M333 262C333 337 270 397 193 397S54 337 54 262S116 127 193 127S333 187 333 262Z" id="g54-74"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="385" vert-adv-y="385"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,4.163,1.006)"><path d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z" id="g113-81"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="617" vert-adv-y="617"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,16.339,0)"><path d="M531 71V127L115 310L531 494V550L57 335V285L531 71ZM531 -40V10H57V-40H531Z" id="g117-93"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="587" vert-adv-y="587"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,28.076,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,34.58,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="228" vert-adv-y="228"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,37.668,0)"><path d="M241 635C89 635 35 457 35 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id="M86" style="vertical-align:-3.993601pt" version="1.1" viewbox="-0.0498162 -10.5264 53.0403 14.52" width="53.0403pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0095,0,0,-0.0095,0,-5.984)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z" id="g50-43"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,6.314,1.006)"><path d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z" id="g113-81"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="617" vert-adv-y="617"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,18.49,0)"><path d="M531 71V127L115 310L531 494V550L57 335V285L531 71ZM531 -40V10H57V-40H531Z" id="g117-93"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="587" vert-adv-y="587"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,30.228,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,36.731,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="228" vert-adv-y="228"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,39.82,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,46.323,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z" id="g113-54"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g></svg> DM versus <svg height="12.3101pt" id="M87" style="vertical-align:-3.427739pt" version="1.1" viewbox="-0.0498162 -8.88236 47.5889 12.3101" width="47.5889pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z" id="g190-69"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="735" vert-adv-y="735"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,9.754,0)"><path d="M861 0V28C774 35 771 41 768 147L759 509C756 612 762 614 851 622V650H681L449 149L221 650H57V622C148 613 153 609 144 479L130 271C123 166 117 123 111 88C104 46 85 34 26 28V0H259V28C192 35 169 42 167 90C166 130 166 173 170 256L185 541H187L411 7H431L675 555H679L683 147C683 41 680 35 598 28V0H861Z" id="g190-78"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="891" vert-adv-y="891"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,21.908,3.264)"><path d="M329 433H203L239 587L230 596L147 534L123 433H57L30 395L34 388H115L61 129C37 16 59 -12 85 -12C147 -12 222 58 260 98L241 125C212 95 160 62 144 62C132 62 127 71 138 126L192 386L305 394L329 433Z" id="g50-117"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="347" vert-adv-y="347"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,25.199,3.264)"><path d="M556 331V384H55V331H556ZM556 140V193H55V140H556Z" id="g54-34"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,30.994,3.264)"><path d="M453 623H65C60 580 56 530 46 472H80C103 538 110 548 175 548H389C310 380 195 168 90 0L98 -12L175 -2C273 206 366 408 462 610L453 623Z" id="g50-56"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,35.614,3.264)"><path d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z" id="g50-51"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,41.841,3.264)"><path d="M513 0V26C455 31 447 37 447 103V278C447 398 390 449 309 449C255 449 202 412 166 376V712C127 700 67 684 19 677V653C85 647 87 643 87 580V103C87 37 79 31 19 26L18 0H231V26C171 32 166 39 166 103V341C194 373 232 392 270 392C337 392 368 351 368 269V103C368 38 360 32 302 26V0H513Z" id="g190-105"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="534" vert-adv-y="534"></glyph.data></g></svg>, CARN versus <svg height="12.3101pt" id="M88" style="vertical-align:-3.427739pt" version="1.1" viewbox="-0.0498162 -8.88236 47.5889 12.3101" width="47.5889pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z" id="g190-69"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="735" vert-adv-y="735"></glyph.data></g><g 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28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z" id="g113-81"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="617" vert-adv-y="617"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,16.339,0)"><path d="M531 71V127L115 310L531 494V550L57 335V285L531 71ZM531 -40V10H57V-40H531Z" id="g117-93"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="587" vert-adv-y="587"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,28.076,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,34.58,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="228" vert-adv-y="228"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,37.668,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,44.172,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z" id="g113-54"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g></svg> CARN versus DM.</div>

Oxidative Medicine and Cellular Longevity

fig7

Figure 7

Figure 7: Potential Therapeutic Role of L-Carnitine in Skeletal Muscle Oxidative Stress and Atrophy Conditions 