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CHIP protects against cardiac pressure overload through regulation of AMPK

, : CHIP protects against cardiac pressure overload through regulation of AMPK. Journal of Clinical Investigation 123(8): 3588-3599

Protein quality control and metabolic homeostasis are integral to maintaining cardiac function during stress; however, little is known about if or how these systems interact. Here we demonstrate that C terminus of HSC70-interacting protein (CHIP), a regulator of protein quality control, influences the metabolic response to pressure overload by direct regulation of the catalytic α subunit of AMPK. Induction of cardiac pressure overload in Chip-/- mice resulted in robust hypertrophy and decreased cardiac function and energy generation stemming from a failure to activate AMPK. Mechanistically, CHIP promoted LKB1-mediated phosphorylation of AMPK, increased the specific activity of AMPK, and was necessary and sufficient for stress-dependent activation of AMPK. CHIP-dependent effects on AMPK activity were accompanied by conformational changes specific to the α subunit, both in vitro and in vivo, identifying AMPK as the first physiological substrate for CHIP chaperone activity and establishing a link between cardiac proteolytic and metabolic pathways.


PMID: 23863712

DOI: 10.1172/JCI69080

Other references

Reddy, P.S., 1977: Ophthalmic use of a new synthetic suture-Dexon. Indian Journal of Ophthalmology 24(4): 9-12

Kroes, Y., 1963: Pig breeding in Denmark.. An outline is given of the history of the state-recognised pig breeding centres and pig performance testing stations in Denmark, their aims, and their effect on pig improvement. At the breeding centres for Danish Landrace pigs the av. number of pi...

Claassen, N.; Steingrobe, B., 1999: Mechanistic simulation models for a better understanding of nutrient uptake from soil. The soil-root system is described including its properties and the processes relating to nutrient uptake. Based on these principles several models of differing complexity are developed, tested and evaluated. The models are tested using data from e...

Bjorum N.; Rafaelsen O.J., 1977: Psycho pharmacologic compendium. This book is one of a series intended to facilitate an understanding of problems in the treatment of patients with psychiatric diseases such as schizophrenia, paranoid psychoses, depressions and alcoholism. This volume is concerned with drugs avai...

Kögler, G.; Somville, T.; Göbel, U.; Hakenberg, P.; Knipper, A.; Fischer, J.; Adams, O.; Krempe, C.; McKenzie, C.; Rüttgers, H.; Meier, W.; Bellmann, O.; Streng, H.; Ring, A.; Rosseck, U.; Rocha, V.; Wernet, P., 1999: Haematopoietic transplant potential of unrelated and related cord blood: the first six years of the EUROCORD/NETCORD Bank Germany. To date, human umbilical cord blood (CB) has been employed successfully in well over 1000 allogeneic (unrelated and sibling) stem cell transplantations. Because of primary limitations in volume and cell numbers, over 90% of these transplantations...

Cobbaert, C.; Kampmann, M.; Katus, H.A.; Kimman, G.P.; Mueller Bardorff, M.; Schoolmann, S.; Rauscher, T.; Van Domburg, R.T.; Zerback, R.; Simoons, M.L., 1997: Time-dependent diagnostic sensitivities of a troponin T bedside test for the detection of acute myocardial infarction and minor myocardial damage in the CCU. European Heart Journal 18(ABSTR SUPPL ): 243

Ackerknecht, E., 1949: Haustierkrankheiten als Gefahr fur den Menschen (Anthropozoonosen). Vierteljahrsschrift der Naturforschenden Gesellschaft in Zurich, 941: 64-65

Brophy, A.L., 1997: MMPI and MMPI-2 scores on the Cook-Medley Hostility Scale. Raw-score means of the Cook-Medley Hostility scale are smaller in the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) normative group than in the MMPI normative group, and T scores are larger. The results contrast with those for the clinica...

Yaretzky, A.; Steiner, Z.; Klajman, A., 1974: Hyperlipemia and pancreatitis due to the contraceptive pill. Harefuah 87(5): 205-206

Diveeva F.K.; Lents M.N., 1968: Concerning post infection immunity during tetanus mouse human. Zhurnal Mikrobiologii Epidemiologii i Immunobiologii 45(6): 123-126