role of HSPs in muscle protein synthesis

[Dr.Dave1]

1: Eur J Appl Physiol. 2006 Mar;96(5):572-80. Epub 2005 Dec 22. Links
Post-exercise leg and forearm flexor muscle cooling in humans attenuates endurance and resistance training effects on muscle performance and on circulatory adaptation.
Yamane M, Teruya H, Nakano M, Ogai R, Ohnishi N, Kosaka M.

The influence of regular post-exercise cold application to exercised muscles trained by ergometer cycling (leg muscles) or handgrip exercise using a weight-loaded handgrip ergometer (forearm flexor muscles) was studied in human volunteers. Muscle loads were applied during exercise programs three to four times a week for 4-6 weeks. Besides measuring parameters characterizing muscle performance, femoral and brachial artery diameters were determined ultrasonographically. Training effects were identified by comparing pre- and post-training parameters in matched groups separately for the trained limbs cooled after exercise by cold-water immersion and the corresponding trained limbs kept at room temperature. Significant training effects were three times more frequent in the control than in the cold group, including increases in artery diameters in the control but not in the cold group. It is concluded that training-induced molecular and humoral adjustments, including muscle hyperthermia, are physiological, transient and essential for training effects (myofiber regeneration, muscle hypertrophy and improved blood supply). Cooling generally attenuates these temperature-dependent processes and, in particular, hyperthermia-induced HSP formation. This seems disadvantageous for training, in contrast to the beneficial combination of rest, ice, compression and elevation in the treatment of macroscopic musculo-tendinous damage.

post workout cooling blunts HSP

1: Biochem Biophys Res Commun. 2007 Jun 22;358(1):331-5. Epub 2007 Apr 30. Links
Geranylgeranylaceton induces heat shock protein 72 in skeletal muscle cells.
Goto K, Kojima A, Morioka S, Naito T, Akema T, Matsuba Y, Fujiya H, Sugiura T, Ohira Y, Yoshioka T.

Effects of an antiulcer drug, geranylgeranylaceton (GGA), and/or heat-stress on 72 kDa heat shock protein (HSP72) expression and protein content in cultured skeletal muscle cells were studied. Mouse skeletal muscle cells (C(2)C(12)) were subjected to either 1) control (cultured at 37 degrees C without GGA), 2) GGA administration (10(-11) - 10(-8) M), 3) heat-stress at 41 degrees C for 60 min, or 4) GGA administration combined with heat-stress. Expression of HSP72 was up-regulated by GGA administration. Heat-stress further enhanced the GGA-related up-regulation of HSP72. Administration of GGA caused an increase of muscular protein content as a dose-dependent manner. Protein synthesis was also stimulated by heat-stress alone in myotubes. It was suggested that GGA stimulates the differentiation of myoblasts and protein synthesis. These observations may also suggest that the administration of GGA could be one of the useful tools to gain muscular mass not only in athletes, but also in patients during rehabilitation.

GGA increases HSP and increases protein synthesis

1: J Appl Physiol. 2006 May;100(5):1679-87. Epub 2005 Dec 29. Links
Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans.
Fischer CP, Hiscock NJ, Basu S, Vessby B, Kallner A, Sj?berg LB, Febbraio MA, Pedersen BK.

Increased levels of reactive oxygen and nitrogen species, as seen in response to exercise, challenge the cellular integrity. Important protective adaptive changes include induction of heat shock proteins (HSPs). We hypothesized that supplementation with antioxidant vitamins C (ascorbic acid) and E (tocopherol) would attenuate the exercise-induced increase of HSP72 in the skeletal muscle and in the circulation. Using randomization, we allocated 21 young men into three groups receiving one of the following oral supplementations: RRR-alpha-tocopherol 400 IU/day + ascorbic acid (AA) 500 mg/day (CEalpha), RRR-alpha-tocopherol 290 IU/day + RRR-gamma-tocopherol 130 IU/day + AA 500 mg/day (CEalphagamma), or placebo (Control). After 28 days of supplementation, the subjects performed 3 h of knee extensor exercise at 50% of the maximal power output. HSP72 mRNA and protein content was determined in muscle biopsies obtained from vastus lateralis at rest (0 h), postexercise (3 h), and after a 3-h recovery (6 h). In addition, blood was sampled for measurements of HSP72, alpha-tocopherol, gamma-tocopherol, AA, and 8-iso-prostaglandin-F2alpha (8-PGF2alpha). Postsupplementation, the groups differed with respect to plasma vitamin levels. The marker of lipid peroxidation, 8-iso-PGF2alpha, increased from 0 h to 3 h in all groups, however, markedly less (P < 0.05) in CEalpha. In [n]Control, skeletal muscle HSP72 mRNA content increased 2.5-fold [/b](P < 0.05) and serum HSP72 protein increased 4-fold (P < 0.05) in response to exercise, whereas a significant increase of skeletal muscle HSP72 protein content was not observed (P = 0.07). In CEalpha, skeletal muscle HSP72 mRNA, HSP72 protein, and serum HSP72 were not different from Control in response to exercise. In contrast, the effect of exercise on skeletal muscle [b]HSP72 mRNA and protein, as well as circulating HSP72, was completely blunted in CEalphagamma[b]. The results indicate that gamma-tocopherol comprises a potent inhibitor of the exercise-induced increase of HSP72 in skeletal muscle as well as in the circulation.

vitamin E (gamma-tocopherol ) blunts HSP expression

[kieltyka34]

nice find on the GGA..

also, I'm assuming timing of ingestion of vit E doesn't matter (because its fat soluble?) with regards to inhibition of HSP increase?

[Dr.Dave1]

1: Acta Physiol Scand. 2003 May;178(1):61-72. Links
Exercise-induced HSP27, HSP70 and MAPK responses in human skeletal muscle.
Thompson HS, Maynard EB, Morales ER, Scordilis SP.

AIM: The present work examined protein and messenger RNA (mRNA) expression of intramuscular heat shock protein 27 (HSP27), heat shock cognate (HSC70) and HSP70 in human biceps brachii (BB) and vastus lateralis (VL) subsequent to two different exercises. METHODS: Untrained subjects performed 50 high-force eccentric contractions with their non-dominant BB and ran downhill (-10 degrees) for 30 min. The 48-h PX stress response was evaluated with immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Muscle damage was indicated indirectly at 48 h post-exercise (PX) [loss of mobility, muscle soreness and serum creatine kinase (CK) activity]. RESULTS: On the protein level, HSP27 and HSP70 increased significantly PX in the BB (384 and 227%, respectively; P < 0.01), but there were no significant HSP changes in the VL or in HSC70 in either muscle. The RT-PCR data complemented these findings: BB HSP27 and HSP70C mRNA levels increased (135 and 128%, respectively; P < 0.05); in the VL only HSP70B increased (206%; P < 0.05). Phosphorylation of e-jun NH2-terminal kinase (JNK) and extracellular regulated kinase (ERK) increased significantly in the BB (226 and 200%, respectively; P < 0.05) but not in the VL, indicating activation of these pathways only after the resistance exercise. CONCLUSION: These data indicate that the PX HSP and mitogen-activated protein kinase responses are exercise-specific and local, not systemic. Further, only the resistance exercise induced HSP expression (protein and mRNA) and JNK/ERK activation at 48 h PX, suggesting that these molecules may be important to long-term skeletal muscle adaptations such as hypertrophy.

HSP increased by resistance training but not aerobic training in untrained individuals

1: Am J Physiol Regul Integr Comp Physiol. 2007 May 23; [Epub ahead of print] Links
Maximal eccentric exercise induces a rapid accumulation of small heat shock proteins on myofibrils and a delayed HSP70 response in humans.
Paulsen G, Vissing K, Kalhovde JM, Ugelstad I, Bayer ML, Kadi F, Schjerling P, Hall?n J, Raastad T.

In this study the stress protein response to unaccustomed maximal eccentric exercise in humans was investigated. Eleven healthy males performed 300 maximal eccentric actions with the quadriceps muscle. Biopsies from vastus lateralis were collected at 30 minutes, 4, 8, 24, 96, and 168 hours after exercise. Cellular regulation and localization of HSP27, alphaB-crystallin and HSP70 were analyzed by immunohistochemistry, ELISA technique and western blotting. Additionally, mRNA levels of HSP27, alphaB-crystallin and HSP70 were quantified by Northern blotting. Thirty minutes after exercise 81+/-8% of the myofibers showed strong HSP27 staining (p<0.01) that gradually decreased during the following week. alphaB-crystallin mimicked the changes observed in HSP27. Thirty minutes after exercise the ELISA analysis showed a 49+/-13% reduction of the HSP27 level in the cytosolic fraction (p<0.01), while western blotting revealed a 15-fold increase of the HSP27 level in the myofibrillar fraction (p<0.01). The cytosolic HSP70 level increased to 203+/-37% of control level 24 hours after exercise (p<0.05). After four days, myofibrillar-bound HSP70 had increased ~10-fold (p<0.01) and was accompanied by strong staining on cross sections. mRNA levels of HSP27, alphaB-crystallin and HSP70 were all elevated the first day after exercise (p<0.01); HSP70 mRNA showed the largest increase (20-fold at eight hours). HSP27 and alphaB-crystallin seemed to respond immediately to maximal exercise by binding to cytoskeletal/myofibrillar proteins, probably to function as stabilizers of disrupted myofibrillar structures. Later, mRNA and total HSP protein levels, especially HSP70, increased, indicating that HSPs play a role in skeletal muscle recovery and remodeling/adaptation processes to high-force exercise. Key words: stress proteins, muscle damage, skeletal muscle.

HSP27 and HSP70 increase in response to resistance training; HSP 70 maixmal increase over control was delayed until 4D post exercise

Acta Physiol (Oxf). 2007 May 3; [Epub ahead of print]Links
Elevated core and muscle temperature to levels comparable to exercise do not increase heat shock protein content of skeletal muscle of physically active men.
Morton JP, Maclaren DP, Cable NT, Campbell IT, Evans L, Bongers T, Griffiths RD, Kayani AC, McArdle A, Drust B.

Aim: Exercise-associated hyperthermia is routinely cited as the signal responsible for inducing an increased production of heat shock proteins (HSPs) following exercise. This hypothesis, however, has not been tested in human skeletal muscle. The aim of the present study was to therefore investigate the role of increased muscle and core temperature in contributing to the exercise-induced production of the major HSP families in human skeletal muscle. Methods: Seven physically active males underwent a passive heating protocol of 1 h duration during which the temperature of the core and vastus lateralis muscle were increased to similar levels to those typically occurring during moderately demanding aerobic exercise protocols. One limb was immersed in a tank containing water maintained at approximately 45 degrees C whilst the contra-lateral limb remained outside the tank and was not exposed to heat stress. Muscle biopsies were obtained from the vastus lateralis of both legs immediately prior to and at 48 h and 7 days post-heating. Results: The heating protocol induced significant increases (P < 0.05) in rectal (1.5 +/- 0.2 degrees C) and muscle temperature of the heated leg (3.6 +/- 0.5 degrees C). Muscle temperature of the non-heated limb showed no significant change (P > 0.05) following heating (pre: 36.1 +/- 0.5, post: 35.7 +/- 0.2 degrees C). Heating failed to induce a significant increase (P > 0.05) in muscle content of HSP70, HSC70, HSP60, HSP27, alphaB-crystallin, MnSOD protein content or in the activity of superoxide dismutase and catalase. Conclusions: These data demonstrate that increases in both systemic and local muscle temperature per se do not appear to mediate the exercise-induced production of HSPs in human skeletal muscle and suggest that non-heat stress factors associated with contractile activity are of more importance in mediating this response.

in active males heating alone does not elicit an increase in HSPs

[Dr.Dave1]

Dig Dis Sci. 2007 Apr 3; [Epub ahead of print] Links
Geranylgeranylacetone Induces Cyclooxygenase-2 Expression in Cultured Rat Gastric Epithelial Cells Through NF-kappaB.
Nishida T, Yabe Y, Fu HY, Hayashi Y, Asahi K, Eguchi H, Tsuji S, Tsujii M, Hayashi N, Kawano S.

Geranylgeranylacetone (GGA) effectively protects the gastric mucosa against noxious agents. The precise mechanisms underlying the gastroprotective actions of GGA are not known. To elucidate the precise mechanism of GGA, the effect of GGA treatment on COX-2 expression in rat gastric epithelial (RGM1) cells was investigated. We used a prostaglandin E(2) (PGE(2)) enzyme-linked immunoassay kit and Western blot analysis to measure PGE(2) production and COX-2 induction by GGA treatment in serum-starved RGM1 cells. Gel-shift assay, Western blot analysis, and a reporter assay were performed to determine which COX-2 promoter was involved in GGA-induced COX-2 expression. GGA treatment dose dependently increased COX-2 expression and PGE(2) production. The nuclear factor (NF)-kappaB sites of the COX-2 gene promoter were critical for GGA-mediated COX-2 expression. GGA induces COX-2 expression and increases PGE(2) production in serum-starved RGM1 cells via activation of the NF-kappaB sites of COX-2 gene promoters.

GGA activates COX-2 via NFKB promoter

J Neurotrauma. 2006 Jul;23(7):1164-78. Links
Role of protein kinase C in neuroprotective effect of geranylgeranylacetone, a noninvasive inducing agent of heat shock protein, on delayed neuronal death caused by transient ischemia in rats.
Fujiki M, Hikawa T, Abe T, Uchida S, Morishige M, Sugita K, Kobayashi H.

We evaluated the neuroprotective effect of geranylgeranylacetone (GGA), an antiulcer agent and inducing agent of heat-shock protein (HSP), against the delayed death of hippocampal neurons induced by transient bilateral occlusion of the common carotid artery (CCA) and hypotension (40 mm Hg) lasting for 10 min. To test the hypothesis that orally administered GGA would induce protein kinase C (PKC), leading to the expression of HSP70 and protection against delayed neuronal death (DND), we gave GGA orally to rats in various regimens prior to bilateral occlusion of the CCA, and quantitatively assessed the extent of DND in region CA1 of the hippocampus at 7 days after transient ischemia. Pretreatment with a single oral dose of GGA of 800 mg/kg at 48 h before ischemia significantly attenuated DND (20.0 +/- 3.81 vs. 321.0 +/- 11.01 mm(3); p < 0.05). A similar degree of neuron sparing occurred when GGA was given 2, 4, or 8 days before ischemia. These neuroprotective effects of GGA were prevented by pretreatment with chelerythrine (CHE), a specific inhibitor of PKC, indicating that PKC may mediate GGA-dependent protection against ischemic DND. Oral GGA-induced expression of HSP70 elicited the expression of PKCdelta, and pretreatment with GGA enhanced the ischemia-induced expression of HSP70, both of which effects were prevented by pretreatment with CHE. These results suggest that a single oral dose of GGA induces the expression of PKCdelta and promotes the expression of HSP70 in the brain, and that GGA plays an important role in neuroprotection against DND. Pretreatment with a single oral dose of GGA provides an important tool for exploring the mechanisms of neuroprotection against DND of hippocampal neurons after transient ischemia.

GGA has a neuroprotective effect against ischemia

1: Circulation. 2001 Oct 9;104(15):1837-43. Links
Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and renders protection against ischemia/reperfusion injury in rat heart.
Ooie T, Takahashi N, Saikawa T, Nawata T, Arikawa M, Yamanaka K, Hara M, Shimada T, Sakata T.

BACKGROUND: Induction of heat-shock proteins (HSPs) results in cardioprotection against ischemic insult. Geranylgeranylacetone (GGA), known as an antiulcer agent, reportedly induces HSP72 in the gastric mucosa and small intestine of rats. The present study tested the hypothesis that oral GGA would induce HSP72 in the heart and thus render cardioprotection against ischemia/reperfusion injury in rats. METHODS AND RESULTS: Cardiac expression of HSPs was quantitatively evaluated in rats by Western blot analysis. Ten minutes of whole-body hyperthermia induced HSP72 expression in the rat hearts. A single oral dose of GGA (200 mg/kg) also induced expression of HSP72, which peaked at 24 hours after administration. Therefore, isolated perfused heart experiments using a Langendorff apparatus were performed 24 hours after administration of 200 mg/kg GGA (GGA group) or vehicle (control group). After a 5-minute stabilization period, no-flow global ischemia was given for 20, 40, or 60 minutes, followed by 30 minutes of reperfusion. During reperfusion, the functional recovery was greater and the released creatine kinase was less in the GGA group than in the control group. Electron microscopy findings revealed that the ischemia/reperfusion-induced damage of myocardial cells was prevented in GGA-treated myocytes. CONCLUSIONS: The results suggest that oral GGA is cardioprotective against ischemic insult through its induction of HSP72.

it also protects the heart agains ischemia

[Dr.Dave1]

nice find on the GGA..

also, I'm assuming timing of ingestion of vit E doesn't matter (because its fat soluble?) with regards to inhibition of HSP increase?

I did not see anything specific on timing of vit E but I would say you are probably correct

[HighRevinSi]

Cool findings! We recently discussed HSP's with regards to Free Radical production and Oxidative Stress in a seminar I am taking.

The results between anaerobic and aerobic HSP responses are probable because HSP's are upregulated during hypoxic states (i.e. anaerobic work) and during an inflammatory response. The inflammatory response in resistance training is likely due to systemic microdamage to myofilaments. Thus we would observe the increase in HSP70 following resistance training. HSP's are very important in that they are chaperone proteins, An upregulation of HSP's is a good protective mechanism for maintaining the stability of protein molecules during remodeling and repair to ensure that proper folding occurs. HSP's seem to be similar to DNA enzymes that ensure proper encoding occurs and that shape and integrity are maintained to promote optimal functioning. Just thought I'd throw in a littler additional info

[Dr.Dave1]

Cool findings! We recently discussed HSP's with regards to Free Radical production and Oxidative Stress in a seminar I am taking.

The results between anaerobic and aerobic HSP responses are probable because HSP's are upregulated during hypoxic states (i.e. anaerobic work) and during an inflammatory response. The inflammatory response in resistance training is likely due to systemic microdamage to myofilaments. Thus we would observe the increase in HSP70 following resistance training. HSP's are very important in that they are chaperone proteins, An upregulation of HSP's is a good protective mechanism for maintaining the stability of protein molecules during remodeling and repair to ensure that proper folding occurs. HSP's seem to be similar to DNA enzymes that ensure proper encoding occurs and that shape and integrity are maintained to promote optimal functioning. Just thought I'd throw in a littler additional info

thanks for the additional info

[capt.blue]

great stuff on HSPs on the previous emails..I also heard from a gnc guy that you can go on www.mri-performance.com they have info on there about their product...which has the patented tex oe in it and has human studies done with it,,,

Theres a lot of info out there that sounds like HSPs can play a role in building muscle, hopefully MRI landed on a hot product thats for real and not some fluffy muffin mix that MT put out...

[Austin109]

great stuff on HSPs on the previous emails..I also heard from a gnc guy that you can go on www.mri-performance.com they have info on there about their product...which has the patented tex oe in it and has human studies done with it,,,

Theres a lot of info out there that sounds like HSPs can play a role in building muscle, hopefully MRI landed on a hot product thats for real and not some fluffy muffin mix that MT put out...

your a shill. all 3 of your posts reguard HSPs and MRI while knocking MT's new product. I have no issue with reps but not informing people of your affiliation is bull****.

[capt.blue]

relax...just like sounds of HSP and MRI is the only one out with the product, besides MT. And MT has loads of caffeine, not a fan of MT and its products...never have been. sorry, but I was just passing on some info. i just found out about. that gnc guy was pumping up the product, may he secretly works for MRI?